Human Physiology Part 4

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Human Physiology Part 4

  1. 1. Neural Control Mechanisms Section A<br />John Paul L. Oliveros, MD<br />
  2. 2. Neural Tissue<br />Neuron: <br />basic unit of the nervous system<br />Serves as integrators<br />Neurotransmitters: <br />chemical messengers released by nerve cells<br />Parts:<br />Cell body<br />Dendrites<br />Axon<br />Axon terminals<br />
  3. 3. Neural Tissue<br />Parts of a neuron<br />Cell Body<br />Contains nucleus and ribosomes<br />Genetic information and machinery for protein synthesis<br />Dendrites<br />Receive inputs from other neurons<br />Branching increases the cell’s receptive surface area<br />Axon<br />AKA nerve fiber<br />Single long process that extends from the cell body to its target cells<br />INITIAL SEGMENT<br />AKA axon hillock<br />Portion of axon closest to the cell body plus parts of the cell body<br />“Trigger zone”<br />Collaterals<br />Main branches of the axon<br />Axon Terminal<br />Ending of each branch of axon<br />Releases neurotransmitters<br />Varicosities<br />Bulging areas along the axon<br />Also releases neurotransmitters<br />
  4. 4. Neural Tissue<br />Myelin Sheath<br />Layers of plasma membrane wrapped around the axon by a nearby supporting cell<br />Speeds up conduction of electrical signals along the axons and conserves energy<br />Oligodendroglia: CNS<br />Schwann cells: PNS<br />Nodes of Ranvier<br />Spaces between adjacent sections of myelin<br />Axons plasma is exposed to ECF<br />
  5. 5. Neural Tissue<br />Axon Transport<br />Movement of various organelles and materials from cell body to axon and its terminal<br />To maintain structure and function of the axon<br />Microtubules<br />Rails along which transport occurs<br />Linking proteins<br />Link organelles and materials to microtubules<br />Function as motors of axon transport and ATPase enzymes<br />Provide energy from split ATP to the motors<br />Axon Terminalcell body<br />Opposite route of transport<br />Route for growth factors and other chemical signals picked up at the terminals<br />Route of tetanus toxins and polio and herpes virus<br />
  6. 6. Neural Tissue<br />
  7. 7. Neural Tissue<br />synapse<br />Specialized junction between two neurons where one alters the activity of the other<br />Presynaptic neuron<br />Conducting signals toward a synapse<br />Postsynaptic neuron<br />Conducts signals away from a synapse<br />
  8. 8. Neural tissue<br />Glial Cells/Neuroglia<br />90% of cells in the CNS<br />Occupy only 50% of CNS<br />Physically and metabolically support neurons<br />Types:<br />Oligodendroglia<br />Form myelin covering of CNS axons<br />Astroglia<br />Regulate composition of ECF in the CNS<br />Remove K+ ions and neurotransmitters around syapses<br />Sustain neurons metabolically (provide glucose and remove ammonia)<br />Embryo: guide neuron migration and stimulate neuron growth<br />Many neuron like characteristics<br />Microglia<br />Perform immune functions in te CNS<br />Schwann cells<br />Glial cells of the PNS<br />Produce myelin sheath of the peripheral nerve fibers<br />
  9. 9. Neural Growth and degeneration<br />Embryo:<br />Precursor cells: develop into neurons or glial cells<br />Neuron cell migrates to its final location and sends out processes<br />Growth cone: specialized tip of axons that finds the correct route and final target of the processes<br />Neurotropic factors: growth factors for neural tissue in the ECF surrounding the growth cone or distant target<br />Synapses are then formed once target tissues are reached<br />Neural development occurs in all trimesters of pregnancy and upto infancy permanent damage by alcohol, drugs, radiation, malnutrition, and viruses<br />Fine tuning:<br />Degeneration of neurons and synapses after growth and projection of axons<br />50-70% of neurons die by apoptosis<br />Refining of connectivity in the nervous system<br />
  10. 10. Neural growth and regeneration<br />Neuron damage<br />Outside CNS<br />Does not affect cell body<br />Severed axon can repair itself and regain significant function<br />Distal axons degenerates<br />Proximal axon develops growth cone and grows back to target organ<br />Within CNS<br />No significant regeneration of the axon occurs at the damage site<br />No significant return of function<br />
  11. 11. Section B<br />Membrane Potentials<br />
  12. 12. Basic principles of electricity<br />Electric potential<br />Potential of work obtained when separated electric charges of opposite signs are allowed to come together <br />Potential differences/potential<br />Difference in the amount of charge between two points<br />Volts: unit of electric potential<br />Millivolts: measurement in biological systems<br />Current<br />Movement of electric charge<br />Depends on the potential differences between charges and the material on which they are moving<br />Resistance<br />Hindrance to electric charge movement<br />Ohms law: <br />I= E/R<br />Insulator<br />Materials with high electrical resistance<br />Conductor<br />Materials with low electrical resistance<br />e.g. water<br />
  13. 13. Resting Membrane Potential<br />Resting membrane potential<br />The potential difference across the plasma membrane under resting conditions<br />Inside cell: negative charge (-70mV)<br />
  14. 14. Resting membrane potential<br />Magnitude of membrane potential is determined by:<br />Differences of specific ion concentrations in the intracellular and extracellular fluids<br />Differences in membrane permeabilities to the different ions<br />
  15. 15. Resting membrane potential<br />Equilibrium potential: <br />the membrane potential at which flux due to concentration gradient is equal to the flux due to electrical potential but at opposite directions<br />No net movement of ion because opposing fluxes are equal<br />Membrane potential will not undergo further change<br />Its value depends on the concentration gradient of an ion across the membrane<br />
  16. 16. Resting membrane potential<br />
  17. 17. Resting Membrane Potential<br />In a resting cell, Na+ and K+ ion concentrations don’t change because the ions moved in and out by the Na+,K+-atpase pump equals that moved by the membrane channels electrical potential across membranes remain constant<br />Electrogenic pump<br />Pump that moves net charge across the membrane and contributes to the membrane potential<br />Na+,K+-ATPase pump:<br />Sends out 3 Na+ ions for moving in 2K+ ions<br />Makes the inside of the cell more negative<br />
  18. 18. Graded Potentials and Action Potentials<br />Nerve cells transmit and process information through transient changes in the membrane potential from it s resting level<br />Two forms of signals<br />Graded potential<br />Over short distances<br />Action potential<br />Long distance signals<br />Depolarized<br />Potential is less negative than the resting level<br />Overshoot<br />A reversal of the membrane potential polarity<br />Cell inside becomes positive relative to the outside<br />Repolarize<br />When the depolarized membranepotential returns toward the resting value<br />hyperpolarize<br />The potential is more negative than the resting lavel<br />
  19. 19. Graded potential<br />Changes in the membrane potential confined to a relatively small region of the plasma membrane<br />Die out within 1-2 mm of site<br />Produced by a specific change in the cell’s environment acting on a specialized region of the membrane<br />Magnitude of the potential change can vary<br />Local current is decremental<br />Amplitude decreases with increasing distance from the origin<br />
  20. 20. Graded Potential<br />
  21. 21. Graded Potential<br />
  22. 22. Action Potentials<br />Rapid and large alterations in the membrane potential <br />100mV from -70mV then reporalize to its resting membrane<br />Excitable membranes: <br />Plasma membranes capable of producing action potentials<br />e.g. Neurons, muscle cells, endocrine cells, immune cells, reproductive cells<br />Only cells in the body that can conduct action potentials<br />Excitability:<br />Ability to generate action potentials<br />
  23. 23. Ionic basis of action potentials<br />Resting state:<br />K+ and Cl- ion membranes open<br />Close to K+ equilibrium<br />Depolarizing phase<br />Opening of voltage-gated Na+ channels 100x<br />More + Na ions enter the cell<br />May overshoot: inside on the cell becomes positvely charged<br />Short duration of action potentials<br />Resting membrane returns rapidly to resting potential because<br />Na+ channels undergo inactivation near the peak of the action potential to then close<br />Voltage gated K+ channels begin to open<br />
  24. 24. Ionic basis of action Potentials<br />Afterhyperpolarization<br />Small hyperpolarization of the membrane potential beyond the resting level<br />Some of voltage gated K+ ions are still open after all Na+ have closed<br />Chloride permeability does’t change during action potential<br />The amount of ions involve is extremely small and produces infinitesimal changes in the intracellular ion concentration<br />Na+,K+-ATPase pump makes sure that concentration gradient of each ions are restored to generate future action potentials<br />
  25. 25. Mechanism of ion-channel changes<br />1st part of depolarization: <br />Due to local current opens up voltage gated channels sodium influx  increase in cell’s positive charge  increase depolarization (positive feedback)<br />Delayed opening of K+ channels<br />Inactivation of Na+ channels:<br />Due to change in the conformation channel proteins<br />Local anesthetics<br />e.g. Procaine, lidocaine<br />Block voltage gated Na+ channels<br />Prevent sensation of pain<br />Animal toxins:<br />Puffer fish: tetrodotoxin<br />Prevent na+ component of action potential<br />In some cells: Ca++ gates open prolonged action potential<br />
  26. 26. Threshold and the all-or-none response<br />The event that initiates the membrane depolarization provides an ionic current that adds positive charge to the inside of the cell<br />Events:<br />K+ efflux increases<br />Due to weaker inside negativity<br />Na+ influx increases<br />Opening of voltage gated channels by initial depolarization<br />As depolarization increaes mor voltage gated channels open<br />Na+influx eventually exceeds K+ efflux positive feedback starts action potential<br />Threshold potential<br />Membrane potential when the net movement of positive charge through ion channels is inward<br />Action potential only occurs after this is reached<br />About 15mV less neative than <br />Threshold Stimuli <br />strong enough to depolarize the membrane to threshold potential<br />Subthreshold potentials<br />Weak depolarizations<br />Membrane returnsto resting level as soon as stimuli is removed<br />No action potential generated<br />Subthreshold stimulus<br />Stimuli that causes subthreshold potentials<br />
  27. 27. Threshold and the all-or-none response<br />Stimuli more than threshold magnitude elicit action potentialswith exactly the same amplitude with that of a threshold stimulus<br />Threshold: <br />membrane events not dependent on stimulus strength<br />Depolarization generates action potential because the positive feedback is operating<br />All-or-none response<br />Action potentials occur maximally or they do not occur at all<br />Firing of the gun analogy<br />
  28. 28. Refractory periods<br />Absolute refractory period<br />During action potential, a 2nd stimulus, no matter how strong, will not produce a 2nd action potential<br />Na+ channels undergo a closes and inactive state at the peak of the action potential<br />Membrane must be repolarized to return Na+ channels to a state which they can be opened again<br />Relative refractory period<br />Interval followng the refractory period during which a 2nd action potential can be produced<br />Stimulus must be greater than usual<br />10-15ms longer in neurons<br />Coincides with the period of hyperpolarization<br />Lingering inactivation of Na+ channels and increased number of potassium channels open<br />Additional action potentials fired<br />Depolarization exceeds the increased threshold<br />Depolarization outlasr the refractory period<br />
  29. 29. Action Potential Propagation<br />The difference in potentials betwen active and resting regions causes ions to flow<br />Local current depolarizes the membrane adjacent to the action potential site to its threshold potential producing another action potential action potential propagation<br />Gunpowder trail analogy<br />Action potentials are not conducted decrementally<br />Direction of the propagation is away from a region of the membrane that has been recently active<br />Due to refractory period<br />
  30. 30. Action potential propagation<br />Muscle cells<br />Action potentials are initiated near the middle of these cylindrical cells and propagate towards the 2 ends<br />Nerve cells<br />Initiation at one end and propagate towards the other end<br />Velocity of action potential propagation depends on<br />Fiber diameter<br />The larger, the faster<br />Myelination<br />Myelin is an insulator<br />Action potential only in the nodes of ranvier<br />Concentration of Na+ channels is high<br />Saltatory conduction/ jumping of action potentials from one node to the other as they propagate <br />Faster conduction<br />
  31. 31. Initiation of action potential<br />Afferent neurons<br />Initial depolarization threshold achieved by a graded potential (receptor potential) generated by sensory receptors at the peripheral ends<br />Efferent neurons/ interneurons<br />Depolarization threshold due to<br />Graded potential generated by synaptic input <br />Spontaneous change in the neurons membrane potential (pacemaker potential)<br />Occurs in absence of external stimuli<br />e.g. Smooth muscle, cardiac muscles<br />Contnuous change in membrane permeability no stable resting membrane potential<br />Implicated in breathing, heart beat, GIT movements<br />
  32. 32.
  33. 33. Section C<br />Synapses<br />
  34. 34. Synapses<br />Anatomically specialized junction between 2 neurons<br />Electrical activity of a presynaptic neuron influences the elcetrical/metabolic activity of a postsynaptic neuron<br />100 quadrillion synapses in the CNS<br />Excitatory synapse<br />Membrane potential of postsynaptic neurons is brought closer to the threshold<br />Inhibitory synapse<br />Postsynaptic neuron membrane potential is brought further away from the threshold or stabilized<br />Convergence<br />Neural input from many neurons affect one neuron<br />Divergence<br />Neural input from one neuron affects many other neurons <br />
  35. 35. Functional anatomy of synapses<br />2 types of synapses:<br />Electrical synapses<br />Pre and postsynaptic cells joined by gap junctions<br />Numerous in cardiac and smooth muscle cells<br />Rare in mammalian nervous system<br />Chemical synapses <br />Synaptic cleft<br />Separates pre and post synaptic neurons<br />Prevents direct propagation of electric current<br />Signals transmitted by means of neurotransmitter<br />Co-transmitters<br />Additional neurotransmitter simultaneously released with another neurotransmitter<br />Synaptic vesicles<br />Store neurotransmitter in the terminals<br />
  36. 36. Functional anatomy of synapses<br />Presynaptic cell:<br />Action potential axon terminal depolarization  voltage-gated Ca++ channels open Ca++ enters  fusion of synaptic vesicles to PM  release of transmitters by exocytosis<br />Postsynaptic cell:<br />Binding of neurotransmitters to receptors  opening or closing of specific ligand sensitive -ion channels<br />One way conduction across synapses in general<br />Brief synaptic delay (0.2 sec) from action potential at presynaptic neuron to membrane potential changes in post synaptic cell<br />
  37. 37. Functional anatomy of synapses<br />Fate of unbound neurotransmitters<br />Are actively transported back to the axon terminal/glial cells<br />Diffuse away from the receptor site<br />Enzymatically transformed into ineffective substances <br />2 kinds of chemical synapse<br />Excitatory<br />Response is depolarization<br />Open postsynaptic-membrane ion channels permeable to positvely charged ions<br />Excitatatory postsynaptic potential (EPSP)<br />Potential change wherien there is net movemnt of positively charge ions into the cell to slightly depolarize it<br />Graded potential to bring the postsynaptic neuron closer to threshold<br />Inhibitory<br />Lessens likelihood for depolarization and action poterntial<br />Opening of Cl- or sometimes K+ channels<br />Inhibitory postsynaptic potential (IPSP)<br />Hyperpolarizing graded potential<br />
  38. 38. Activation of a postsynaptic cell<br />In most neurons, one excitatory synaptic event by itself is not enough to cause threshold to be reached in the postsynaptic neuron<br />Temporal summation:<br />Axon stimulated before the 1st EPSP has died away<br />The 2nd EPSP adds to the previous one and creates a greater input than from 1 input alone<br />Input signals arrive at the same cell at different times<br />The potentials summate because there is a greater number of open ion channels<br />Spatial summation:<br />2 inputs occured at different locations on the same cell<br />
  39. 39. Activation of a postsynaptic cell<br />
  40. 40. Synaptic effectiveness<br />A presynaptic terminal does not release a constant amount of neurotransmitters everytime it is activated<br />Presynaptic synapse (axon-axon synapse)<br />Axon terminal of one ends on an axon terminal of another <br />Effects:<br />Presynaptic inhibition<br />Decrease the amount of neurotransmitter secreted <br />Presynaptic facilitation<br />Increase the amount of neurotransmitter secreted<br />
  41. 41. Modification of Synaptic transmission by Drugs and Disease<br />All synaptic mechanisms are vulnerable to drugs<br />Agonist:<br />Drugs that bind to a receptor and produces a response similar to normal activation of a receptor<br />Antagonis:<br />Drugs that bind to the receptor but aren’t able to activate it<br />Diseases:<br />Tetanus toxin<br />Protease that destroys certain proteins in the synaptic-vesicle docking mechanism of inhibitory neurons to neurons supplying the skeletal muscle<br />Botulinum toxin and spider venom<br />Affect neurotransmitter release from synaptic vesicles<br />Interfere with docking proteins<br />Act on axons different from those acted upon by tetanus toxin<br />
  42. 42. Synaptic effectiveness<br />
  43. 43. Neurotransmitters and Neuromodulators<br />Neuromodulators<br />Messengers that cause complex responses/modulation<br />Alter effectiveness of synapse<br />Modify postsynaptic cell’s response to neurotransmitters<br />Change the presynaptic cell’s release, release, re-uptake, or metabolism of a transmitter<br />Receptors for neuromodulators bring about changes in the metabolic processes in neurons via G-proteins<br />Changes occur within minutes, hours, or days<br />enzyme activity<br />Protein synthesis<br />Associated with slower events<br />Learning <br />Development<br />Motivational states<br />Sensory/motor activities<br />
  44. 44. Neurotransmitters and neuromodulators<br />Acetylcholine (ACh)<br />Synthesized from choline and acetyl coenzyme A<br />Reducing enzyme: acetylcholinesterase<br />Mostly in the PNS, also in CNS<br />Nerve fibers: cholinergic<br />Receptors: nicotinic, muscarinic<br />Function: attention, learning, memory<br />Pathology: Alzheimers<br />Biogenic amines<br />Synthesized from AA and contain an amino group<br />MC: dopamine, norepinphrine, serotonin, histamine<br />Epinephrine: biogenic amine hormone secreted by adrenal medulla<br />Norepinephrine: important neurotransmitter in CNS and PNS<br />
  45. 45. Neurotransmitters and neuromodulators<br />Catecholamines<br />Dopamine, norepinephrine, epinephrine<br />Contain a catechol ring and an amine group<br />Synthesized from tyrosine<br />Reducing enzyme: Monoamine oxidase <br />Catecholamine releasing neurons mostly in brainstem and hypothalamus but axons go to all parts of the CNS<br />Function: state of consciousness, mood, motivation, directed attention, movement, blood-pressure regulation, and hormone release<br />Catecholamines<br />Fibers: adrenergic, noradrenergic<br />Receptors: Alpha, Beta<br />Further divide in Alpha1, alpha2, Beta1 and Beta2 receptors<br />
  46. 46. Neurotransmitters and neuromodulators<br />
  47. 47. Neurotransmitters and neuromodulators<br />Serotonin<br />Biogenic amine synthesized from trytophan<br />Effects have slow onset and innervate virtually every structure of the brain and spinal cord.<br />Has 16 different receptor types<br />Function:<br />Motor: excitatory<br />Sensation: inhibitory<br />Lowest activity during sleep and highest during alert wakefulness<br />Motor activity, sleep, food intake, reproductive behavior, mood and anxiety<br />Present in non-neural cells (e.g. Platelets, GI tract, immune system)<br />Amino Acid Neurotransmitters<br />Amino acids that function as neurotransmitters<br />Most prevalent neurotransmitter in the CNS and affect virtually all neurons there<br />Excitatory Amino Acids <br />Glutamate<br />Aspartate<br />Function: learning, memory, neural development<br />Pathology: epilepsy, alzheimers, parkinsons disease,<br />Neural damage after stroke, brain trauma<br />Drugs: phencylidine (angel dust)<br />Inhibitory Amino Acids<br />GABA (gamma-aminobutyric acid)<br />Glycine<br />Drugs: valium<br />
  48. 48. Neurotransmitters and neuromodulators<br />Neuropeptides<br />Composed of 2 or more AA linked together by peptide bonds<br />Function as hormones or paracrine agents<br />Synthesis: from large proteins produced by ribosomes<br />Fibers: peptidergic<br />Endogenous opioids<br />B-endorphin, dynorphins, enkephalins<br />Receptors are site of action of opiate drugs (morphine, codeine)<br />Function: analgesia, “jogger’s high”, eating and drinking behavior, CVS regulation, mood and behavior<br />Substance P<br />Released by afferent neurons<br />Relay sensory information into the CNS<br />Nitric Oxide<br />Diffuse into the intracellular fluid of nearby cells from cells of origin<br />Messenger between neurons and effector cells<br />Activate cGMP<br />Function: learning, development, drug tolerance, penile erection, sensory and motor modulation<br />ATP<br />Very fast acting excitatory transmitter<br />Adenine<br />

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