This document summarizes key concepts in neuromuscular physiology. It discusses the electrochemical basis of nerve conduction including resting membrane potential, action potentials, and ion channels. It describes the properties of excitable tissues like neurons and muscle. Factors contributing to resting membrane potential and the roles of ion channels and the sodium-potassium pump are explained. The generation and propagation of action potentials, as well as the structure and function of synapses, ionotropic receptors, and neurotransmitters are outlined. The document concludes by covering neuromuscular junction structure and function, including acetylcholine synthesis, receptor activation, and muscle contraction via calcium signaling.
This document provides an overview of neuromuscular physiology, including nerve conduction, the resting membrane potential, action potentials, ion channels, propagation of action potentials, the neuromuscular junction, factors that influence excitability, ionic gradients, and the sodium-potassium pump. It also discusses neuromuscular blocking agents, their mechanisms of action, and disorders that affect the neuromuscular junction.
This document discusses neuromuscular physiology, specifically nerve conduction and the neuromuscular junction. It covers topics such as:
- Resting membrane potential and how ion channels, the sodium-potassium pump, and ion concentration gradients contribute to it
- How action potentials are generated through the opening of voltage-gated sodium and potassium channels
- Propagation of action potentials along myelinated and unmyelinated nerves
- The role of the neuromuscular junction, including acetylcholine synthesis and release, and how it activates nicotinic receptors on the postsynaptic membrane
- How neuromuscular blocking drugs like tubocurarine and succinylcholine work by competitively or depress
This document discusses neuromuscular physiology, specifically focusing on nerve conduction, the resting membrane potential, action potentials, propagation of action potentials, and the neuromuscular junction. It covers topics like ion channels, the sodium-potassium pump, factors contributing to the resting membrane potential, ionic channels, propagation of action potentials, the neuromuscular junction, neuromuscular blocking agents, and disorders of the neuromuscular junction.
This document provides an overview of neurophysiology topics covered in an MD Psych course, including:
1. Electrophysiology, neurotransmitters, sensory and motor systems, higher functions, and memory/emotions
2. Details of the resting membrane potential, action potential generation, and propagation
3. Synapse structure and function, including neurotransmitter release and postsynaptic responses
4. Physiology of the neuromuscular junction, including acetylcholine release and endplate potentials
The document summarizes key aspects of physiology of the nervous system. It discusses:
1) Functional subdivisions of the nervous system including sensory, motor, integrative, and autonomic functions.
2) Topics covered including action potentials, nerve impulse transmission, neuromuscular junction, and physiology of sensory and motor functions.
3) Excitable tissues having a more negative resting membrane potential than non-excitable tissues due to ion distributions and channels that facilitate potassium efflux and sodium/potassium pumping.
4) Generation of action potentials relies on voltage-gated sodium and potassium channels opening and closing to cause depolarization, repolarization, and hyperpolarization for signal propagation along myelinated and un
This document provides an overview of neurophysiology and neuromuscular physiology. It discusses topics such as electrophysiology, sensory functions, physiology of pain, the motor system, sleep and arousal, memory and emotions. It then focuses on neuromuscular physiology, covering nerve conduction, the neuromuscular junction, muscle contraction, nerve fibre types, and neuromuscular blocking agents.
Excitable tissues like neurons and muscles have a resting membrane potential of -70mV due to ion gradients established by pumps and permeability. An action potential occurs when the membrane reaches a threshold for opening voltage-gated sodium channels, causing rapid depolarization to +30mV then repolarization as potassium channels open. This propagates along membranes to transmit signals. The sodium-potassium pump restores ion gradients for the next action potential.
This document provides an overview of neuromuscular physiology, including nerve conduction, the resting membrane potential, action potentials, ion channels, propagation of action potentials, the neuromuscular junction, factors that influence excitability, ionic gradients, and the sodium-potassium pump. It also discusses neuromuscular blocking agents, their mechanisms of action, and disorders that affect the neuromuscular junction.
This document discusses neuromuscular physiology, specifically nerve conduction and the neuromuscular junction. It covers topics such as:
- Resting membrane potential and how ion channels, the sodium-potassium pump, and ion concentration gradients contribute to it
- How action potentials are generated through the opening of voltage-gated sodium and potassium channels
- Propagation of action potentials along myelinated and unmyelinated nerves
- The role of the neuromuscular junction, including acetylcholine synthesis and release, and how it activates nicotinic receptors on the postsynaptic membrane
- How neuromuscular blocking drugs like tubocurarine and succinylcholine work by competitively or depress
This document discusses neuromuscular physiology, specifically focusing on nerve conduction, the resting membrane potential, action potentials, propagation of action potentials, and the neuromuscular junction. It covers topics like ion channels, the sodium-potassium pump, factors contributing to the resting membrane potential, ionic channels, propagation of action potentials, the neuromuscular junction, neuromuscular blocking agents, and disorders of the neuromuscular junction.
This document provides an overview of neurophysiology topics covered in an MD Psych course, including:
1. Electrophysiology, neurotransmitters, sensory and motor systems, higher functions, and memory/emotions
2. Details of the resting membrane potential, action potential generation, and propagation
3. Synapse structure and function, including neurotransmitter release and postsynaptic responses
4. Physiology of the neuromuscular junction, including acetylcholine release and endplate potentials
The document summarizes key aspects of physiology of the nervous system. It discusses:
1) Functional subdivisions of the nervous system including sensory, motor, integrative, and autonomic functions.
2) Topics covered including action potentials, nerve impulse transmission, neuromuscular junction, and physiology of sensory and motor functions.
3) Excitable tissues having a more negative resting membrane potential than non-excitable tissues due to ion distributions and channels that facilitate potassium efflux and sodium/potassium pumping.
4) Generation of action potentials relies on voltage-gated sodium and potassium channels opening and closing to cause depolarization, repolarization, and hyperpolarization for signal propagation along myelinated and un
This document provides an overview of neurophysiology and neuromuscular physiology. It discusses topics such as electrophysiology, sensory functions, physiology of pain, the motor system, sleep and arousal, memory and emotions. It then focuses on neuromuscular physiology, covering nerve conduction, the neuromuscular junction, muscle contraction, nerve fibre types, and neuromuscular blocking agents.
Excitable tissues like neurons and muscles have a resting membrane potential of -70mV due to ion gradients established by pumps and permeability. An action potential occurs when the membrane reaches a threshold for opening voltage-gated sodium channels, causing rapid depolarization to +30mV then repolarization as potassium channels open. This propagates along membranes to transmit signals. The sodium-potassium pump restores ion gradients for the next action potential.
- Nerve and muscle cells are excitable tissues that respond to stimuli through generation of electrical impulses.
- Nerve cells called neurons transmit signals through electrical impulses called action potentials. Action potentials are generated when the membrane potential rapidly changes from resting potential to threshold potential.
- At chemical synapses, an action potential causes release of neurotransmitters which may excite or inhibit the next neuron. Summation of multiple synaptic signals can trigger action potentials in post-synaptic neurons.
This document summarizes the fundamental types and properties of neurons. It discusses the three main types of neurons: sensory neurons that detect changes, interneurons that process information, and motor neurons that send signals to muscles and glands. It also describes the basic structures of neurons like the cell body, dendrites, and axon. Additionally, it explains the electrical signaling properties of neurons including resting membrane potential, action potentials, and synaptic transmission between neurons.
Neurotransmitters are chemical messengers that are released by neurons to transmit signals between neurons or from neurons to effector cells. They are stored in synaptic vesicles and released into the synaptic cleft upon arrival of an action potential. Common neurotransmitters include acetylcholine, monoamines like dopamine and norepinephrine, amino acids, peptides, and gaseous transmitters. Neurotransmitters bind to receptors on the postsynaptic membrane, which can be ionotropic and directly open ion channels, or metabotropic and activate second messenger systems. Summation of excitatory and inhibitory postsynaptic potentials determines whether an action potential is initiated in the postsynaptic cell.
This document discusses synaptic transmission and neurotransmitters. It begins by describing the structure and function of synapses, including the roles of presynaptic and postsynaptic membranes. It then explains excitatory and inhibitory postsynaptic potentials. The document also discusses the neuromuscular junction, how acetylcholine is released and binds to nicotinic receptors to trigger muscle contraction. Finally, it outlines several major neurotransmitters - acetylcholine, glutamate, and GABA - including their receptors, mechanisms of action, and effects on synaptic transmission.
This document provides an overview of neurotransmission and biochemistry of cell signaling. It discusses the structure and function of neurons, ion channels, synaptic transmission, and various neurotransmitters. Key points covered include the resting potential of neurons, action potentials, voltage-gated ion channels, neurotransmitter synthesis and release, and postsynaptic receptor types including ligand-gated and G-protein coupled receptors. Neurotransmitters discussed include acetylcholine, catecholamines, serotonin, GABA and glutamate.
The document discusses the nervous system and synapses. It describes how synapses allow neurons to communicate via either electrical or chemical transmission. At chemical synapses, neurotransmitters are released from the presynaptic neuron and bind to receptors on the postsynaptic neuron, causing changes in its membrane potential. Excitatory synapses cause depolarization via EPSPs, while inhibitory synapses cause hyperpolarization or stabilization via IPSPs. Spatial and temporal summation of EPSPs at synapses can bring the postsynaptic neuron to threshold to fire an action potential. Neurotransmitters are removed from synapses via reuptake or degradation to terminate signals. Drugs can modify synaptic transmission by affecting neurotransmitter synthesis, storage, release, receptor activation, or reupt
The neuromuscular junction (NMJ) is a synapse between a motor neuron and skeletal muscle fiber. At the NMJ:
1) Motor neurons release acetylcholine into the synaptic cleft when an action potential arrives, which binds to receptors on the muscle fiber membrane.
2) This opens ion channels, allowing sodium ions to flow in and initiate an action potential in the muscle fiber, causing contraction.
3) The NMJ uses acetylcholine as its neurotransmitter and acetylcholine receptors to transmit signals from motor neurons to muscles in a precisely regulated process.
A synapse is a small gap at the end of a neuron that allows a signal to pass from one neuron to the next. Neurons are cells that transmit information between your brain and other parts of the central nervous system. Synapses are found where neurons connect with other neurons.
Synapses are key to the brain's function, especially when it comes to memory.Synapses connect neurons and help transmit information from one neuron to the next. When a nerve signal reaches the end of the neuron, it cannot simply continue to the next cell. Instead, it must trigger the release of neurotransmitters which can then carry the impulse across the synapse to the next neuron.
Once a nerve impulse has triggered the release of neurotransmitters, these chemical messengers cross the tiny synaptic gap and are taken up by receptors on the surface of the next cell.
These receptors act much like a lock, while the neurotransmitters function much like keys. Neurotransmitters may excite or inhibit the neuron they bind to Synapses are composed of three main parts:
The presynaptic ending that contains neurotransmitters
The synaptic cleft between the two nerve cells
The postsynaptic ending that contains receptor sites
An electrical impulse travels down the axon of a neuron and then triggers the release of tiny vesicles containing neurotransmitters. These vesicles will then bind to the membrane of the presynaptic cell, releasing the neurotransmitters into the synapse.
Synaptic transmission types I Steps of chemical neurotransmission I Nervous S...HM Learnings
Synaptic transmission between neurons occurs either electrically or chemically. In electrical transmission, gap junctions allow ions to pass directly between neurons. In chemical transmission, neurotransmitters are released from vesicles in the presynaptic neuron and bind to receptors in the postsynaptic neuron. The process involves neurotransmitter synthesis, storage in vesicles, calcium-triggered release, binding to receptors, and termination of signaling via reuptake or enzymatic degradation. Chemical transmission is slower but allows for signal modulation, in contrast to electrical transmission.
The document summarizes key concepts in neurophysiology including:
1) Resting potentials are maintained by ion gradients and the sodium-potassium pump, keeping the intracellular environment negatively charged.
2) Action potentials are rapid shifts in membrane potential triggered by the opening of voltage-gated sodium channels, which then allow voltage-gated potassium channels to repolarize the neuron.
3) Postsynaptic potentials are graded responses to neurotransmitters that can be excitatory or inhibitory, influencing whether an action potential is triggered in the postsynaptic cell.
This presentation contains the basic information about nerve cells and action potential. This work is done for academic purpose only so if you are using give proper reference.
The synapse is a junction that mediates information transfer between neurons. There are two main types of synapses - chemical synapses, which use neurotransmitters to transmit signals across the synaptic cleft, and electrical synapses, which allow direct electrical coupling between neurons. At chemical synapses, an action potential in the presynaptic neuron causes neurotransmitter release, which then binds to and activates receptors on the postsynaptic neuron, generating excitatory or inhibitory postsynaptic potentials. These signals are then integrated to determine whether the postsynaptic neuron fires an action potential.
The synapse is a junction that mediates information transfer between neurons. There are two main types of synapses - chemical synapses, which use neurotransmitters to transmit signals across the synaptic cleft, and electrical synapses, which allow direct electrical coupling between neurons. At chemical synapses, an action potential in the presynaptic neuron causes neurotransmitter release, which then binds to and activates receptors on the postsynaptic neuron. The effects of neurotransmitters are then terminated through degradation or reuptake. Summation of synaptic potentials determines whether an action potential is generated in the postsynaptic neuron.
This document discusses the neuromuscular junction. It describes the structure including the presynaptic terminal, synaptic cleft, and postsynaptic membrane containing nicotinic acetylcholine receptors. Transmission involves presynaptic calcium influx and vesicle release of acetylcholine, binding to receptors to produce an endplate potential, and hydrolysis by acetylcholinesterase. Disorders like myasthenia gravis and Lambert-Eaton syndrome are outlined. Finally, neuromuscular blockers and stimulators are classified by their mechanisms of action.
This document discusses excitable tissues and their resting membrane potential and action potentials. It begins by defining excitable tissues as those capable of generating and transmitting electrochemical impulses along their membranes, such as nerves and muscles. It then explains that excitable tissues maintain a more negative resting membrane potential than non-excitable tissues due to ion distributions and gradients established by ion pumps and channels. When an excitable cell is stimulated past its threshold, voltage-gated sodium channels open, allowing sodium to rush in and depolarize the membrane. This triggers voltage-gated potassium channels to then repolarize the membrane, before the sodium-potassium pump restores ion gradients. This process propagates as an action potential along the
This document provides an overview of the anatomy and physiology of the neuromuscular junction (NMJ). It discusses the key components of the NMJ including the motor neuron, synaptic cleft, and motor endplate. It describes how acetylcholine is synthesized, stored in vesicles, released into the synaptic cleft upon nerve stimulation, and binds to acetylcholine receptors on the motor endplate to induce muscle contraction. The document also discusses quantal theory, vesicle recycling, acetylcholinesterase function, and different types of neuromuscular blocking drug mechanisms like desensitization and channel blockade. Clinical applications involving diseases affecting the NMJ like myasthenia gravis and treatments using neuromuscular blocking agents
This document provides an overview of the anatomy and physiology of the neuromuscular junction (NMJ). It discusses the key components of the NMJ including the motor neuron, synaptic cleft, and motor endplate. It describes how acetylcholine is synthesized, stored in vesicles, released into the synaptic cleft upon nerve stimulation, and binds to acetylcholine receptors on the motor endplate to elicit muscle contraction. The document also discusses quantal theory, vesicle recycling, acetylcholinesterase function, and different types of neuromuscular blocking drug mechanisms like desensitization and channel blockade. Clinical applications involving diseases affecting the NMJ like myasthenia gravis and treatments using neuromuscular blocking agents
- Nerve and muscle cells are excitable tissues that respond to stimuli through generation of electrical impulses.
- Nerve cells called neurons transmit signals through electrical impulses called action potentials. Action potentials are generated when the membrane potential rapidly changes from resting potential to threshold potential.
- At chemical synapses, an action potential causes release of neurotransmitters which may excite or inhibit the next neuron. Summation of multiple synaptic signals can trigger action potentials in post-synaptic neurons.
This document summarizes the fundamental types and properties of neurons. It discusses the three main types of neurons: sensory neurons that detect changes, interneurons that process information, and motor neurons that send signals to muscles and glands. It also describes the basic structures of neurons like the cell body, dendrites, and axon. Additionally, it explains the electrical signaling properties of neurons including resting membrane potential, action potentials, and synaptic transmission between neurons.
Neurotransmitters are chemical messengers that are released by neurons to transmit signals between neurons or from neurons to effector cells. They are stored in synaptic vesicles and released into the synaptic cleft upon arrival of an action potential. Common neurotransmitters include acetylcholine, monoamines like dopamine and norepinephrine, amino acids, peptides, and gaseous transmitters. Neurotransmitters bind to receptors on the postsynaptic membrane, which can be ionotropic and directly open ion channels, or metabotropic and activate second messenger systems. Summation of excitatory and inhibitory postsynaptic potentials determines whether an action potential is initiated in the postsynaptic cell.
This document discusses synaptic transmission and neurotransmitters. It begins by describing the structure and function of synapses, including the roles of presynaptic and postsynaptic membranes. It then explains excitatory and inhibitory postsynaptic potentials. The document also discusses the neuromuscular junction, how acetylcholine is released and binds to nicotinic receptors to trigger muscle contraction. Finally, it outlines several major neurotransmitters - acetylcholine, glutamate, and GABA - including their receptors, mechanisms of action, and effects on synaptic transmission.
This document provides an overview of neurotransmission and biochemistry of cell signaling. It discusses the structure and function of neurons, ion channels, synaptic transmission, and various neurotransmitters. Key points covered include the resting potential of neurons, action potentials, voltage-gated ion channels, neurotransmitter synthesis and release, and postsynaptic receptor types including ligand-gated and G-protein coupled receptors. Neurotransmitters discussed include acetylcholine, catecholamines, serotonin, GABA and glutamate.
The document discusses the nervous system and synapses. It describes how synapses allow neurons to communicate via either electrical or chemical transmission. At chemical synapses, neurotransmitters are released from the presynaptic neuron and bind to receptors on the postsynaptic neuron, causing changes in its membrane potential. Excitatory synapses cause depolarization via EPSPs, while inhibitory synapses cause hyperpolarization or stabilization via IPSPs. Spatial and temporal summation of EPSPs at synapses can bring the postsynaptic neuron to threshold to fire an action potential. Neurotransmitters are removed from synapses via reuptake or degradation to terminate signals. Drugs can modify synaptic transmission by affecting neurotransmitter synthesis, storage, release, receptor activation, or reupt
The neuromuscular junction (NMJ) is a synapse between a motor neuron and skeletal muscle fiber. At the NMJ:
1) Motor neurons release acetylcholine into the synaptic cleft when an action potential arrives, which binds to receptors on the muscle fiber membrane.
2) This opens ion channels, allowing sodium ions to flow in and initiate an action potential in the muscle fiber, causing contraction.
3) The NMJ uses acetylcholine as its neurotransmitter and acetylcholine receptors to transmit signals from motor neurons to muscles in a precisely regulated process.
A synapse is a small gap at the end of a neuron that allows a signal to pass from one neuron to the next. Neurons are cells that transmit information between your brain and other parts of the central nervous system. Synapses are found where neurons connect with other neurons.
Synapses are key to the brain's function, especially when it comes to memory.Synapses connect neurons and help transmit information from one neuron to the next. When a nerve signal reaches the end of the neuron, it cannot simply continue to the next cell. Instead, it must trigger the release of neurotransmitters which can then carry the impulse across the synapse to the next neuron.
Once a nerve impulse has triggered the release of neurotransmitters, these chemical messengers cross the tiny synaptic gap and are taken up by receptors on the surface of the next cell.
These receptors act much like a lock, while the neurotransmitters function much like keys. Neurotransmitters may excite or inhibit the neuron they bind to Synapses are composed of three main parts:
The presynaptic ending that contains neurotransmitters
The synaptic cleft between the two nerve cells
The postsynaptic ending that contains receptor sites
An electrical impulse travels down the axon of a neuron and then triggers the release of tiny vesicles containing neurotransmitters. These vesicles will then bind to the membrane of the presynaptic cell, releasing the neurotransmitters into the synapse.
Synaptic transmission types I Steps of chemical neurotransmission I Nervous S...HM Learnings
Synaptic transmission between neurons occurs either electrically or chemically. In electrical transmission, gap junctions allow ions to pass directly between neurons. In chemical transmission, neurotransmitters are released from vesicles in the presynaptic neuron and bind to receptors in the postsynaptic neuron. The process involves neurotransmitter synthesis, storage in vesicles, calcium-triggered release, binding to receptors, and termination of signaling via reuptake or enzymatic degradation. Chemical transmission is slower but allows for signal modulation, in contrast to electrical transmission.
The document summarizes key concepts in neurophysiology including:
1) Resting potentials are maintained by ion gradients and the sodium-potassium pump, keeping the intracellular environment negatively charged.
2) Action potentials are rapid shifts in membrane potential triggered by the opening of voltage-gated sodium channels, which then allow voltage-gated potassium channels to repolarize the neuron.
3) Postsynaptic potentials are graded responses to neurotransmitters that can be excitatory or inhibitory, influencing whether an action potential is triggered in the postsynaptic cell.
This presentation contains the basic information about nerve cells and action potential. This work is done for academic purpose only so if you are using give proper reference.
The synapse is a junction that mediates information transfer between neurons. There are two main types of synapses - chemical synapses, which use neurotransmitters to transmit signals across the synaptic cleft, and electrical synapses, which allow direct electrical coupling between neurons. At chemical synapses, an action potential in the presynaptic neuron causes neurotransmitter release, which then binds to and activates receptors on the postsynaptic neuron, generating excitatory or inhibitory postsynaptic potentials. These signals are then integrated to determine whether the postsynaptic neuron fires an action potential.
The synapse is a junction that mediates information transfer between neurons. There are two main types of synapses - chemical synapses, which use neurotransmitters to transmit signals across the synaptic cleft, and electrical synapses, which allow direct electrical coupling between neurons. At chemical synapses, an action potential in the presynaptic neuron causes neurotransmitter release, which then binds to and activates receptors on the postsynaptic neuron. The effects of neurotransmitters are then terminated through degradation or reuptake. Summation of synaptic potentials determines whether an action potential is generated in the postsynaptic neuron.
This document discusses the neuromuscular junction. It describes the structure including the presynaptic terminal, synaptic cleft, and postsynaptic membrane containing nicotinic acetylcholine receptors. Transmission involves presynaptic calcium influx and vesicle release of acetylcholine, binding to receptors to produce an endplate potential, and hydrolysis by acetylcholinesterase. Disorders like myasthenia gravis and Lambert-Eaton syndrome are outlined. Finally, neuromuscular blockers and stimulators are classified by their mechanisms of action.
This document discusses excitable tissues and their resting membrane potential and action potentials. It begins by defining excitable tissues as those capable of generating and transmitting electrochemical impulses along their membranes, such as nerves and muscles. It then explains that excitable tissues maintain a more negative resting membrane potential than non-excitable tissues due to ion distributions and gradients established by ion pumps and channels. When an excitable cell is stimulated past its threshold, voltage-gated sodium channels open, allowing sodium to rush in and depolarize the membrane. This triggers voltage-gated potassium channels to then repolarize the membrane, before the sodium-potassium pump restores ion gradients. This process propagates as an action potential along the
This document provides an overview of the anatomy and physiology of the neuromuscular junction (NMJ). It discusses the key components of the NMJ including the motor neuron, synaptic cleft, and motor endplate. It describes how acetylcholine is synthesized, stored in vesicles, released into the synaptic cleft upon nerve stimulation, and binds to acetylcholine receptors on the motor endplate to induce muscle contraction. The document also discusses quantal theory, vesicle recycling, acetylcholinesterase function, and different types of neuromuscular blocking drug mechanisms like desensitization and channel blockade. Clinical applications involving diseases affecting the NMJ like myasthenia gravis and treatments using neuromuscular blocking agents
This document provides an overview of the anatomy and physiology of the neuromuscular junction (NMJ). It discusses the key components of the NMJ including the motor neuron, synaptic cleft, and motor endplate. It describes how acetylcholine is synthesized, stored in vesicles, released into the synaptic cleft upon nerve stimulation, and binds to acetylcholine receptors on the motor endplate to elicit muscle contraction. The document also discusses quantal theory, vesicle recycling, acetylcholinesterase function, and different types of neuromuscular blocking drug mechanisms like desensitization and channel blockade. Clinical applications involving diseases affecting the NMJ like myasthenia gravis and treatments using neuromuscular blocking agents
How to Manage Reception Report in Odoo 17Celine George
A business may deal with both sales and purchases occasionally. They buy things from vendors and then sell them to their customers. Such dealings can be confusing at times. Because multiple clients may inquire about the same product at the same time, after purchasing those products, customers must be assigned to them. Odoo has a tool called Reception Report that can be used to complete this assignment. By enabling this, a reception report comes automatically after confirming a receipt, from which we can assign products to orders.
Elevate Your Nonprofit's Online Presence_ A Guide to Effective SEO Strategies...TechSoup
Whether you're new to SEO or looking to refine your existing strategies, this webinar will provide you with actionable insights and practical tips to elevate your nonprofit's online presence.
Temple of Asclepius in Thrace. Excavation resultsKrassimira Luka
The temple and the sanctuary around were dedicated to Asklepios Zmidrenus. This name has been known since 1875 when an inscription dedicated to him was discovered in Rome. The inscription is dated in 227 AD and was left by soldiers originating from the city of Philippopolis (modern Plovdiv).
3. Excitable tissues
• Excitable tissues have more
negative RMP
( - 70 mV to - 90 mV)
excitable Non-excitable
Red cell
GIT
neuron
muscle
• Non-excitable tissues
have less negative RMP
-53 mV epithelial cells
-8.4 mV RBC
-20 to -30 mV fibroblasts
-58 mV adipocytes
4. Factors contributing to RMP
• One of the main factors is K+ efflux
• (Nernst Equilibrium Potential: -94mV)
• Contribution of Na influx is little
• (Nernst Equilibrium Potential: +61mV)
• Na/K pump causes more negativity inside the
membrane
•
Negatively charged protein remaining inside due to
impermeability contributes to the negativity
• Net result: -70 mV inside
5. Ionic channels
• Leaky channels (leak channels)
– Allow free flow of ions
– K+ channels (large number)
– Na+ channels (fewer in number)
– Therefore membrane is more permeable to K+
6. Na/K pump
• Active transport system for Na-K exchange using
energy
• It is an electrogenic pump since 3 Na efflux coupled
with 2 K influx
• Net effect of causing negative charge inside the
membrane
3 Na+
2 K+
ATP ADP
8. Physiological basis of AP
• When the threshold level is reached
– Voltage-gated Na channels open up
– Since Na conc outside is more than the inside
– Na influx will occur
– Positive ion coming inside increases the positivity of the membrane potential and
causes depolarisation
– When it reaches +35, Na channels closes
– Then Voltage-gated K channels open up
– K efflux occurs
– Positive ion leaving the inside causes more negativity inside the membrane
– Repolarisation occurs
• Na/K pump restores Na and K conc slowly
– By pumping 3 Na ions outward and 2 K ions inward
9. • At rest: the activation gate is closed
• At threshold level: activation gate opens
– Na influx will occur
– Na permeability increases to 500 fold
• when reaching +35, inactivation gate closes
– Na influx stops
• Inactivation gate will not reopen until resting membrane potential is reached
outside
inside
outside
inside
-70 Threshold level +35
Na+ Na+
outside
inside
Na+
m gate
h gate
10. – At rest: K channel is closed
– At +35
• K channel open up slowly
• This slow activation causes K efflux
– After reaching the resting still slow K channels may
remain open: causing further hyperpolarisation
outside
inside
outside
inside
-70 At +35
K+ K+
n gate
11. Refractory Period
• Absolute refractory
period
– During this period nerve
membrane cannot be
excited again
– Because of the closure
of inactivation gate
-70
+30
outside
inside
12. Refractory Period
• Relative refractory
period
– During this period nerve
membrane can be
excited by supra
threshold stimuli
– At the end of
repolarisation phase
inactivation gate opens
and activation gate
closes
– This can be opened by
greater stimuli strength
-70
+30
outside
inside
13. Propagation of AP
• When one area is depolarised
• A potential difference exists between that site
and the adjacent membrane
• A local current flow is initiated
• Local circuit is completed by extra cellular fluid
14. Propagation of AP
• This local current flow will cause opening of
voltage-gated Na channel in the adjacent
membrane
• Na influx will occur
• Membrane is deloparised
15. Propagation of AP
• Then the previous area become repolarised
• This process continue to work
• Resulting in propagation of AP
20. AP propagation along myelinated
nerves
• Na channels are conc around nodes
• Therefore depolarisation mainly occurs at
nodes
21. AP propagation along myelinated
nerves
• Local current will flow one node to another
• Thus propagation of A.P. is faster. Conduction
through myelinated fibres also faster.
• Known as Saltatory Conduction
27. Synapse
• Synapse is a gap between two neurons
• More commonly chemical
• Rarely they could be electrical (with gap junctions)
– which are pores (as shown in the electron micrograph)
constructed of connexin proteins
31. Types of synapses
• Axo-dendritic synapse
• Most common
• Axon terminal branch (presynaptic
element) synapses on a dendrite
• Axo-somatic synapse
• Axon terminal branch synapses on
a soma (cell body)
• Axo-axonic synapse
• Axon terminal branch synapses on
another axon terminal branch (for
presynaptic inhibition)
• Dendro-dendritic synapse
• Dendrite synapsing on another
dendrite (localised effect)
32. Synaptic ultrastructure
• The presynaptic enlargement
(bouton, varicosity, or end
plate) contains synaptic vesicles
(20 nm diameter)
• Pre- and postsynaptic plasma
membranes are separated by a
synaptic cleft (20 nm wide)
• The cleft contains glycoprotein
linking material and is
surrounded by glial cell
processes
Synaptic
proteins
33. Presynaptic events
• Presynaptic membrane contains voltage gated
calcium channels
• Membrane depolarisation opens up Ca2+ channels
• Ca2+ influx will occur
• Neurotransmitter molecules are released in
proportion to the amount of Ca2+ influx, in turn
proportional to the amount of presynaptic
membrane depolarization
34. Details of presynaptic events
• in the resting state, the presynaptic membrane has resting membrane potential
• when an action potential arrives at the end of the axon
• the adjacent presynaptic membrane is depolarised
• voltage-gated Ca2+ channels open and allow Ca2+ influx (driven by [Ca2+] gradient)
• elevated [Ca2+] activates synaptic proteins
(SNARE proteins: Synaptobrevin, Syntaxin, SNAP 25) and triggers vesicle
mobilization and docking with the plasma membrane
• vesicles fuse with presynaptic plasma membrane and release neurotransmitter
molecules (about 5,000 per vesicle) by exocytosis
• neurotransmitter molecules diffuse across the cleft & bind with postsynaptic
receptor proteins
• neurotransmitter molecules are eliminated from synaptic clefts via pinocytotic
uptake by presynaptic or glial processes and/or via enzymatic degradation at the
postsynaptic membrane
• molecules are recycled
• subsequently, presynaptic plasma membrane repolarises
35.
36. Neurotransmitter receptors
• Once released, the neurotransmitter molecules diffuse across
the synaptic cleft
• When they “arrive” at the postsynaptic membrane, they bind to
neurotransmitter receptors
• Two main classes of receptors:
– Ionotropic receptors
– Metabotropic receptors
37. IONOTROPIC RECEPTORS
• Neurotransmitter molecule binds to the receptor
• Cause a ligand-gated ion channel to open
• Become permeable to either sodium, potassium or chloride
• Accordingly depolarisation (excitation) or hyperpolarisation (inhibition)
• Quick action, short lasting
38. • Neurotransmitter attaches to G-protein-coupled receptors (GPCR) which has slower, longer-lasting and
diverse postsynaptic effects
• They can have effects that change an entire cell’s metabolism
• Activates enzymes that trigger internal metabolic change inside the cell
• Activate cAMP
• Activate cellular genes: forms more receptor proteins
• Activate protein kinase: decrease the number of proteins
• Sometimes open up ion channels also
Metabotropic Receptors
39. • Excitation
– 1. Na+ influx cause accumulation of positive charges
causing excitation (eg. Nicotinic Ach receptor)
– 2. Ca2+ influx
– 3. various internal changes to excite cell, increase
in excitatory receptors, decrease in inhibitory
receptors.
40. • Inhibition
– 1. K+ efflux (GABA B receptor)
– 2. Cl- influx (GABA A receptor)
– 3. activation of receptor enzymes to inhibit
metabolic functions or to increase inhibitory
receptors or decrease excitatory receptors
41. • Excitatory effects of neurotransmitters
– EPSP: excitatory post synaptic potential
• Inhibitory effects of neurotransmitters
– IPSP: inhibitory post synaptic potential
42. Postsynaptic activity
• Synaptic integration
– On average, each neuron in the brain receives about 10,000
synaptic connections from other neurons
– Many (but probably not all) of these connections may be
active at any given time
– Each neuron produces only one output
– One single input is usually not sufficient to trigger this output
– The neuron must integrate a large number of synaptic inputs
and “decide” whether to produce an output or not
– Constant interplay of excitatory and inhibitory activity on the
postsynaptic neuron produces a fluctuating membrane
potential that is the algebraic sum of the hyperpolarizing and
depolarizing activities
– Soma of the neuron thus acts as an integrator
43.
44. Other synaptic activities
• Postsynaptic inhibition
– eg. GABA activates GABA A receptors on the postsynaptic
membrane and opens up Cl- channels and causes
hyperpolarisation and inhibition
• Presynaptic inhibition
– eg. GABA activates GABA B receptors on the presynaptic
membrane and through G proten activation opens up K+
channels and causes hyperpolarisation and inhibition
• Autoreceptors
– eg. Ach released from the presynaptic membrane activates
autoreceptors for Ach on the presynaptic membrane and
causes feedback inhibition
• Renshaw cell inhibition
– Spinal motor neuron activates a collalteral neuron which
secrete glycine or GABA and which inhibit activity of the
spinal motor neuron
• Retrograde signalling
– Neurotransmitter secreted from the postsynaptic
membrane act on the receptor on the presynaptic
membrane and through G protein activation causes
inhibition eg. endocannabinoids
45. Forms of Drug Action at the Synapse
• Ways to agonize
– Stimulate release
– Receptor binding
– Inhibition of reuptake
– Inhibition of deactivation
– Promote synthesis
• Ways antagonize
– Block release
– Receptor blocker
– Prevent synthesis
8.
Autoreceptors
46. Dendritic spine
• Small button like extensions like “door knobs”
found on the dendritic processes that contain
post-synaptic densities
• Axo-dendritic synapses terminates in these
• Dendritic spines are known to change shape, to
the extent of appearing and disappearing entirely
& is the basis of memory
• A mechanism underlying memory loss in
Alzheimer's disease involves a loss of dendritic
spines in hippocampal pyramidal cells
• Ca2+ channels, NMDA receptors are present in
these
• Long-term potentiation (LTP) at Hebbian synapses
in hippocampal region CA1 occurs involving NMDA
receptors in these sites
47. NEUROMUSCULAR JUNCTION
Presynaptic terminal (terminal knob,
boutons, end-feet or synaptic knobs)
Terminal has synaptic vesicles and mitochondria
Mitochondria (ATP) are present inside the presynaptic
terminal
Vesicles containing neurotransmitter (Ach)
48. Presynaptic terminal (terminal knob,
boutons, end-feet or synaptic knobs)
Presynaptic membrane contain voltage-gated Ca2+ channels
The quantity of neurotransmitter released is proportional to
the number of Ca2+ entering the terminal
Ca2+ ions binds to the protein molecules on the inner surface
of the synaptic membrane called release sites
Neurotransmitter binds to these sites and exocytosis occur
50. Synthesis of Ach
• Synthesised from choline and acetyl-coenzyme A (acetyl-coA) in the
terminal axoplasm of motor neurons
• Acetyl-coA is synthesised from pyruvate in the mitochondria in the axon
terminals
• Approximately 50% of the choline is extracted from extracellular fluid by a
sodium dependent active transport system
• Other 50% is from acetylcholine breakdown at the neuromuscular junction.
• Majority of the choline originates from the diet with hepatic synthesis only
accounting for a small proportion
51. • Postsynaptic membrane contain nicotinic
acetylcholine receptor
Ach
Na+
• This receptor contains several
sub units (2 alpha, beta, delta &
epsilon)
• Ach binds to alpha subunit
• Na+ channel opens up
• Na+ influx occurs
• End Plate Potential (EPP)
•This is a graded potential
•Once this reaches the threshold
level
•AP is generated at the
postsynaptic membrane
•This is an example of an ionotropic
receptor
52. IONOTROPIC RECEPTORS
• Neurotransmitter molecule (Ach) binds to the receptor (Ach receptor)
• Cause a ligand-gated ion channel (Na+) to open
• Become permeable to either sodium
• Accordingly depolarisation (excitation)
• Quick action, short lasting
53. Ach vesicle docking
• With the help of Ca entering the presynaptic terminal
• Docking of Ach vesicles occur
• Docking:
– Vesicles move toward & interact with membrane of
presynaptic terminal
• There are many proteins necessary for this purpose
• These are called SNARE proteins
• eg. Syntaxin, synaptobrevin etc
54. Muscle contraction
• Depolarisation of the muscle membrane
spreads through the muscle
• Causes muscle contraction
• Excitation - contraction coupling
– Excitation : electrical event
– Contraction : mechanical event
55. Ryanodine receptor (RyR)
• This is a receptor located in the sarcoplasmic
reticulum which provide calcium necessary for
muscle contraction
• Ryanodine receptor releases Ca2+ from
sarcoplasmic reticulum
• Ca2+ flows to the myoplasm in the vicinity of actin &
myosin
• These receptors are essential for excitation-
contraction coupling
• Ryanodine receptors are also known to be present
in the cardiac muscle and brain (hippocampus)
• Dysfunctional RyR-mediated Ca2+ handling has
been implicated in the pathogenesis of heart failure,
cardiac arrhythmias, skeletal myopathies, diabetes,
and neurodegenerative diseases.
• Cognitive dysfunction may be related to RyR
induced calcium release In Alzheimer’s and PTSD
56. • Ca++ binds to troponin
• Troponin shifts tropomyosin
• Myosin binding sites in actin filament
uncovered
• Myosin head binds with actin
• Cross bridges form
• Filaments slide with ATP being broken down
• Muscle shortens
• New ATP occupies myosin head
• Myosin head detaches
• Filaments slide back
• Cycling continues as long as Ca is available
Troponin
Actin
Myosin
Tropomyosin
ATP
57. • Relaxation
– This occurs when Ca++ is removed from myoplasm
by Ca++ pump located in the sarcoplasmic
reticulum
– When Ca++ conc is decreased
– Troponin returns to original state
– Trpomyosin covers myosin binding sites
– Cross-bridge cycling stops
58. Slow twitch fibre (type I fibre)
– Slow cross-bridge cycling
– slow rate of shortening (eg. soleus muscle in calf)
– high resistance to fatigue
– high myoglobin content
– high capillary density
– many mitochondria
– low glycolytic enzyme content
– They are red muscle fibres
– eg. Marathon runners
59. Fast twitch fibre (type II fibre)
– rapid cross-bridge cycling,
– rapid rate of shortening (eg. extra-
ocular muscles)
– low resistance to fatigue
– low myoglobin content
– low capillary density
– few mitochondria
– high glycolytic enzyme content
– fast twitch fibers use anaerobic
metabolism to create fuel, they are
much better at generating short bursts
of strength or speed than slow
muscles
– eg. sprinter
60. NMJ blocking
• Useful in general anaesthesia to facilitate inserting tubes
• Muscle paralysis is useful in performing surgery
• Commonly used to paralyze patients requiring intubation
whether in an emergency as a life-saving intervention or for a
scheduled surgery and procedure
• To assist with mechanical ventilation in patients who have
reduced lung compliance
• Indications for intubation during an emergency
– failure to maintain or protect the airway
– failure to adequately ventilate or oxygenate
– anticipation of a decline in clinical status
61. Earliest known NMJ blocker - Curare
• Curare has long been used in South America as
an extremely potent arrow poison
• Darts were tipped with curare and then
accurately fired through blowguns made of
bamboo
• Death for birds would take one to two minutes,
small mammals up to ten minutes, and large
mammals up to 20 minutes
• NMJ blocker used in patients is tubocurarine
• Atracurium is now used
62. Non-depolarising blocking agents
– eg.
• Curare
• Atracurium
• Rocuronium
• Vencuronium
– Competitive
– Act by competing with Ach for the Ach receptors
– Binds to Ach receptors and blocks
– Prevent Ach from attaching to its receptors
– No depolarisation
– Late onset, prolonged action
– 70–80% of receptors should be occupied to produce an effect
– To produce complete block, at least 92% of receptors must be occupied
– Ach can compete & the effect overcomes by an excess Ach
– Anticholinesterases can reverse the action
63. Depolarising blocking agents
– eg. Succinylcholine
– non-competitive, chemically act like Ach
– Bind to motor end plate and once depolarises
– Persistent depolarisation leads to a block
• Due to inactivation of Na channels
– Ach cannot compete with depolarising blockers
– There are two phases in the depolarising block
– Phase I block and Phase II block
– Phase I block (depolarisation block)
• After a depolarizing agent binds to the motor end plate receptor, the
agent remains bound and thus the end plate cannot repolarize
• During this depolarizing phase the transient muscle fasciculation
occur
• Absence of fade to tetanic stimulation
• Prolonged exposure to succinylcholine leads to desensitisation block.
– This occurs when ACh receptors are insensitive to the channel-opening effects of
agonists, including ACh itself.
64. Depolarising blocking agents
– Phase II block
• This occurs after repeated boluses or a prolonged infusion of
succinylcholine
• After adequate depolarization has occurred, phase II sets in and the
muscles are no longer receptive to acetylcholine released by the
motor neurons
• After the initial depolarization, the membrane potential gradually
returns towards the resting state, even though the neuromuscular
junction is still exposed to the drug. Neurotransmission remains
blocked throughout.
• It is at this point that the depolarizing agent has fully
achieved paralysis
• Fade after tetanic stimulation
– Succinylcholine has quick action start within 1 min and last for 12 min
– Hydrolysed by plasma cholinesterase (also called pseudocholinesterase)
produced in the liver
– Prolonged blockade is seen in liver disease or pregnancy
– Inhibition of plasma cholinesterase occurs with OP compounds
– Side effect: hyperkalaemia
– Bind to nicotinic and muscarinic Ach, causes bradycardia
– Contraindicated in burns
68. Repolarized
PHASE II
Membrane repolarizes
but the receptor is
desensitized to effect
of acetylcholine
+ + + +
- - - -
+ + + +
- - - -
- - - -
+ + + +
- - - -
+ + + +
Depolarizing Neuromuscular blocking drugs
69. Anticholinesterases
• AchE inhibitors
– Inhibit AchE so that Ach accumulates and causes
depolarising block
• Reversible
– Competitive inhibitors of AChE
– Block can be overcome by curare
• physostigmine, neostigmine, edrophonium
• Irreversible
– Binds to AChE irreversibly
• , insecticides, nerve gases
70. Reversal of NMJ blockers
• Recovery from the effects of non-depolarising relaxants can
occur spontaneously by elimination of the agent either
unchanged or after metabolism
• However, this process may be slow, of variable time and cannot
be reliably predicted
• Pharmacological antagonism or reversal of NMJ block is
therefore indicated in clinical practice
• Anticholinesterases (eg. Neostigimine) reverse the action of
non-depolarising blockers
• Another drug (eg. sugammadex) which bind to non-depolarising
blocker and reverses its action is used
• There is no antagonist for succinylcholine but its action is short
lasting
71. NMJ disorders
• Myasthenia gravis (MG)
– Antibodies to Ach receptors
– Post synaptic disorder
• Lambert Eaton myasthenic syndrome (LEMS)
– Presynaptic disorder (antibodies against Ca channels)
• Neuromyotonia (Isaac’s syndrome)
– Down-regulation of K+ channels, hyperexcitability due to prolonged
depolarisation
• Botulism
– Presynaptic disorder
– Binds to the presynatic region, cleaves SNARE proteins and prevent
release of Ach
• Tetanus
– Presynaptic disorder
– Blockade of neurotransmitter release (GABA & glycine) of spinal
inhibitory neurons causes hyper-excitable tetanic muscle contractions
72. Botulinum toxin
• Most potent neurotoxin known
• Produced by bacterium Clostridium botulinum
• Causes severe diarrhoeal disease called botulism
• Action:
– enters into the presynaptic terminal
– cleaves proteins (syntaxin, synaptobrevin) necessary for Ach vesicle
release with Ca2+
• Chemical extract is useful for reducing muscle spasms, muscle
spasticity and even removing wrinkles (in plastic surgery)
73.
74. Organophosphates
• Phosphates used as insecticides
• Action
– AchE inhibitors
– Therefore there is an excess Ach
accumulation
– Depolarising type of postsynaptic
block
• Used as a suicidal poison
• Causes muscle paralysis and death
• Nerve gas (sarin)
75. Snake venom
• Common Krait (bungarus
caeruleus)
– Produces neurotoxin known as
bungarotoxin
– Very potent
• Causes muscle paralysis and death
if not treated
• Cobra
– venom contain neurotoxin
76. Myasthenia gravis
• Serious neuromuscular disease
• Antibodies form against acetylcholine nicotinic
postsynaptic receptors at the NMJ
• Characteristic pattern of progressively reduced
muscle strength with repeated use of the muscle and
recovery of muscle strength following a period of rest
• Present with ptosis, fatiguability, speech difficulty,
respiratory difficulty
• Treated with cholinesterase inhibitors
78. Acetylcholine (Ach)
• earliest neurotransmitter discovered
• secreted at the following sites
– neuromuscular junction (skeletal muscle contraction excitatory)
– heart (inhibitory)
– autonomic ganglia (both sympathetic and parasympathetic)
– adrenal medulla
– parasympathetic postganglionic nerve endings
– central pathways in the brain (neocortex, hippocampus) and basal forebrain
(cognition, memory, arousal, attention)
– brainstem (REM sleep)
– large pyramidal cells of the motor cortex
– basal ganglia (striatum)
• receptors
– nicotinic (NN: autonomic ganglia, NM: NMJ) – ionotropic receptors Na+ influx
– muscarinic (parasympathetc terminal)
• sub types: M1, M2, M3, M4, M5
• metabotropic receptors with G protein and second messenger cAMP and K+
channel opening
79. Acetylcholine (Ach)
Clinical aspects
• NMJ blockers (postsynaptic blocker): competitive blocker (atracurium) &
depolarising blocker (succinylcholine)
• atropine – parasympathetic blocker, anticholinergic, antimuscarinic actions
• botulinum toxin (food poisoning) – Ach release is blocked presynaptically,
Botox is useful in hemifacial spasms, writer’s cramps, torticollis, dystonia,
plastic surgery
• organophosphate (insecticide poisoning) – anticholinesterase action causing
increased Ach level and depolarising blocking action causing cholinergic
effects, treated with atropine
• Antibodies against Ach receptors in myasthenia gravis – treated with
anticholinesterases (neostigmine, pyridostigmine)
• loss of Ach neurons in Alzheimer’s patients: treated with donepezil and
rivastigmine (anticholinesterases, increases Ach level)
• pilocarpine – muscarinic (M3) cholinergic eye drops are used in glaucoma to
reduce intra-ocular pressure, causes miosis (pupillary constriction) whereas
atropine causes mydriasis (pupillary dilatation)
• anticholinergics are useful in Parkinson disease (to treat tremor)
• anticholinergics causing bronchodilatation useful in COPD
80. Neuromuscular junction in smooth muscle
• There is intrinsic innervation in smooth muscles eg. In GI tract, extrinsic
innervation from autonomic nervous system
• There is no specialized connection between the nerve fiber and the smooth
muscle cell
• The nerve fibers essentially passes "close" to the smooth muscle cells and
releases the neurotransmitter
• The neurotransmitter can bind to any one of the nearby smooth muscle cells
• many different neurotransmitters can be released from the many different
nerves that innervate smooth muscle cells
• They could be excitatory or inhibitory
• eg. Ach, norepinephrine, nitric oxide, prostacyclin, endothelin
• There is nothing equivalent to the motor endplate in smooth muscle,
therefore receptors for the neurotransmitters are located throughout the
smooth muscle membrane
• Smooth muscle can be made to contract by hormones and paracrine agents
81. Channelopathies
• In excitable cells
– periodic paralysis (K+ channel, Na+ channel)
– myasthenia (nicotinic Ach receptor with a ligand Na+
channel)
– myotonia (K+ channel)
– malignant hypothermia (Ryanodine Receptor, a Ca2+
channel),
– long QT syndrome (Na+ and K+ channel)
• In nonexcitable cells
– cystic fibrosis (Cl- channel)
– Bartter’s syndrome (K+ channel)
82. Clinical Scenarios
• A patient presented with right sided weakness
of face, arm and leg
• Questions
• Domains tested
– Knowledge
– Communication
83. Clinical Scenarios
• eg.
A patient presented with right sided weakness
of face, arm and leg
• Questions
• Domains tested
– Knowledge
– Communication