Y1S2 Synapse NMJ Neurotransmitters

6,225 views

Published on

Published in: Health & Medicine, Technology
2 Comments
11 Likes
Statistics
Notes
  • Thanks a lot sir! this way is much easier and effective!
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here
  • thanx sir ,this is very helpful
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here
No Downloads
Views
Total views
6,225
On SlideShare
0
From Embeds
0
Number of Embeds
2
Actions
Shares
0
Downloads
830
Comments
2
Likes
11
Embeds 0
No embeds

No notes for slide

Y1S2 Synapse NMJ Neurotransmitters

  1. 1. Physiology of synapse, neuromuscular junction and neurotransmitters Prof. Vajira Weerasinghe Dept of Physiology Faculty of Medicine University of Peradeniya
  2. 2. What is a synapse? <ul><li>A gap between two neurons </li></ul><ul><li>Mostly chemical </li></ul><ul><li>Rarely electrical </li></ul><ul><ul><li>Mostly present in lower animals </li></ul></ul><ul><ul><li>Gap junctions </li></ul></ul><ul><li>Synapses could be </li></ul><ul><ul><li>Axo-dendritic </li></ul></ul><ul><ul><li>Axo-somatic </li></ul></ul><ul><ul><li>Axo-axonic </li></ul></ul>
  3. 4. Many different types
  4. 5. Basic structure <ul><li>Presynaptic membrane </li></ul><ul><ul><li>Contains neurotransmitter vesicles </li></ul></ul><ul><li>Synaptic cleft </li></ul><ul><li>Postsynaptic membrane </li></ul><ul><ul><li>Contains receptors for the neurotransmitter </li></ul></ul>
  5. 6. Synaptic transmission <ul><li>Action potential passes from the presynaptic neuron to the postsynaptic neuron </li></ul><ul><li>Although an axon conducts both ways, conduction through synapse is one way </li></ul><ul><li>A neuron receives more than 10000 synapses </li></ul><ul><li>Postsynaptic activity is an integrated function </li></ul>
  6. 7. Neurotransmitters <ul><li>Chemicals that facilitate signal transmission across a synapse </li></ul><ul><li>Neurotransmitters are released on the presynaptic side and bind to receptors on the postsynaptic side </li></ul><ul><li>Earliest neurotransmitter discovered was acetylcholine </li></ul><ul><li>There are different chemical types </li></ul><ul><ul><li>Amines </li></ul></ul><ul><ul><ul><li>Norepinephrine, Epinephrine, dopamine, serotonin (5HT), histamine </li></ul></ul></ul><ul><ul><li>Amino acids </li></ul></ul><ul><ul><ul><li>GABA, Glycine, Glutamate, Aspartate </li></ul></ul></ul><ul><ul><li>Peptides </li></ul></ul><ul><ul><ul><li>Beta endorphin, enkephalins, dynorphin </li></ul></ul></ul><ul><ul><li>Others </li></ul></ul><ul><ul><ul><li>Acetylcholine, nitric oxide </li></ul></ul></ul>
  7. 8. Neurotransmitter release <ul><li>“ At rest”, the synapse contains numerous synaptic vesicles filled with neurotransmitter </li></ul><ul><li>Intracellular calcium levels are very low </li></ul><ul><li>Arrival of an action potential causes opening of voltage-gated calcium channels </li></ul><ul><li>Calcium enters the synapse </li></ul><ul><li>Calcium triggers exocytosis and release of neurotransmitter </li></ul><ul><li>Vesicles are recycled by endocytosis </li></ul>
  8. 9. Ca 2+ Ca 2+
  9. 10. Neurotransmitter receptors <ul><li>Once released, the neurotransmitter molecules diffuse across the synaptic cleft </li></ul><ul><li>When they “arrive” at the postsynaptic membrane, they bind to neurotransmitter receptors </li></ul><ul><li>Two main classes of receptors: </li></ul><ul><ul><li>Ligand-gated ion channels </li></ul></ul><ul><ul><ul><li>transmitter molecules bind on the outside, cause the channel to open and become permeable to either sodium, potassium or chloride </li></ul></ul></ul><ul><ul><li>G-protein-coupled receptors </li></ul></ul><ul><ul><ul><li>G-protein-coupled receptors have slower, longer-lasting and diverse postsynaptic effects. They can have effects that change an entire cell’s metabolism </li></ul></ul></ul><ul><ul><ul><li>or an enzyme that activates an internal metabolic change inside the cell </li></ul></ul></ul><ul><ul><ul><li>activate cAMP </li></ul></ul></ul><ul><ul><ul><li>activate cellular genes: forms more receptor proteins </li></ul></ul></ul><ul><ul><ul><li>activate protein kinase: decrease the number of proteins </li></ul></ul></ul>
  10. 11. <ul><li>Excitation </li></ul><ul><ul><li>1. Na + influx cause accumulation of positive charges causing excitation </li></ul></ul><ul><ul><li>2. Decreased K + efflux or Cl - influx </li></ul></ul><ul><ul><li>3. Various internal changes to excite cell, increase in excitatory receptors, decrease in inhibitory receptors. </li></ul></ul>
  11. 12. <ul><li>Inhibition </li></ul><ul><ul><li>1. Efflux of K + </li></ul></ul><ul><ul><li>2. Influx of Cl - </li></ul></ul><ul><ul><li>3. activation of receptor enzymes to inhibit metabolic functions or to increase inhibitory receptors or decrease excitatory receptors </li></ul></ul>
  12. 13. <ul><li>Excitatory effects of neurotransmitters </li></ul><ul><ul><li>EPSP: excitatory post synaptic potential </li></ul></ul><ul><li>Inhibitory effects of neurotransmitters </li></ul><ul><ul><li>IPSP: inhibitory post synaptic potential </li></ul></ul>
  13. 14. Postsynaptic activity <ul><li>Synaptic integration </li></ul><ul><ul><li>On average, each neuron in the brain receives about 10,000 synaptic connections from other neurons </li></ul></ul><ul><ul><li>Many (but probably not all) of these connections may be active at any given time </li></ul></ul><ul><ul><li>Each neuron produces only one output </li></ul></ul><ul><ul><li>One single input is usually not sufficient to trigger this output </li></ul></ul><ul><ul><li>The neuron must integrate a large number of synaptic inputs and “decide” whether to produce an output or not </li></ul></ul>
  14. 15. Neurotransmitters
  15. 16. Acetylcholine (Ach) <ul><ul><li>First neurotransmitter discovered in 1921 </li></ul></ul><ul><ul><li>secreted by motor neurons, autonomic nerves, large pyramidal cells of the motor cortex, basal ganglia (caudate & putamen), hippocampus. </li></ul></ul><ul><ul><li>It is generally excitatory </li></ul></ul><ul><ul><li>receptors </li></ul></ul><ul><ul><ul><li>nicotinic (autonomic ganglia, NMJ) - Na influx </li></ul></ul></ul><ul><ul><ul><li>muscarinic (parasympathetc terminal) </li></ul></ul></ul><ul><ul><ul><ul><ul><li>sub types: M1(brain), M2, M3, M4, M5 </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>second messenger cAMP </li></ul></ul></ul></ul></ul><ul><ul><li>Common Ach blockers: plant poison (curare), botulinum toxin (food poison) </li></ul></ul><ul><ul><li>Loss of Ach neurons in Alzheimer’s patients </li></ul></ul>
  16. 17. Norepinephrine <ul><ul><li>present in the autonomic nerves, brain stem, hypothalamus, locus ceruleus of the pons </li></ul></ul><ul><ul><li>Mostly it causes excitation but sometimes inhibition also happens </li></ul></ul><ul><ul><li>Increases BP and HR </li></ul></ul><ul><ul><li>control the overall activity of the brain and the mood </li></ul></ul><ul><ul><li>receptors </li></ul></ul><ul><ul><ul><li> 1,  2,  1,  2,  3 </li></ul></ul></ul><ul><ul><ul><ul><li>second messenger: cAMP </li></ul></ul></ul></ul>
  17. 18. Dopamine <ul><li>present in the cerebral cortex, hypothalamus </li></ul><ul><li>secreted by neurons in the basal ganglia </li></ul><ul><li>Mainly inhibitory </li></ul><ul><li>Involved in the reward mechanisms in the brain </li></ul><ul><li>Drugs like cocaine, opium, heroin, and alcohol increase the levels of dopamine </li></ul><ul><li>receptors: </li></ul><ul><ul><ul><li>D1, D2, D3, D4, D5 </li></ul></ul></ul><ul><ul><ul><ul><li>second messenger: cAMP </li></ul></ul></ul></ul><ul><li>Increased levels associates with schizophrenia, low levels are associated with Parkinsonism </li></ul>
  18. 19. GABA <ul><li>Present in the basal ganglia </li></ul><ul><li>Also present in the spinal cord, cerebellum & many other areas of the Cortex </li></ul><ul><li>Major inhibitory neurotransmitter of the brain occurring in 30-40% of all synapses </li></ul><ul><li>receptors </li></ul><ul><ul><ul><li>GABA A increase Cl- influx </li></ul></ul></ul><ul><ul><ul><li>GABA B act via G proteins, increase K+ influx </li></ul></ul></ul><ul><li>Low GABA levels are associated with anxiety and epilepsy </li></ul>
  19. 20. Glycine <ul><li>Present in the synapses of the spinal cord, interneurons </li></ul><ul><li>also present in the retina </li></ul><ul><li>Inhibitory (increase Cl influx) </li></ul><ul><li>by its action on NMDA receptors it is excitatory </li></ul>
  20. 21. Glutamate & Aspartate <ul><li>Excitatory amino acids </li></ul><ul><ul><li>glutamate is present in presynaptic terminals in the sensory pathways and other cortical areas </li></ul></ul><ul><ul><li>present in basal ganglia </li></ul></ul><ul><ul><li>Involved in the stretch reflex </li></ul></ul><ul><ul><li>Main excitatory neurotransmitter in brain & spinal cord </li></ul></ul><ul><ul><li>aspartate is present in cortical pyramidal cells & visual cortex </li></ul></ul><ul><ul><li>receptors: metabotropic receptors, kainate, AMPA, NMDA </li></ul></ul><ul><ul><li>NMDA receptors are present in hippocampus, involved in memory & learning </li></ul></ul><ul><ul><li>Increased levels are associated with certain neurological diseases </li></ul></ul>
  21. 22. Serotonin <ul><li>secreted by the nuclei originating in the median raphe of the brain stem and terminate in dorsal horn of the spinal cord and hypothalamus </li></ul><ul><li>Inhibitory </li></ul><ul><li>Control the mood of the person and important in sleep </li></ul><ul><li>also present in GIT, platelets & limbic system </li></ul><ul><li>receptors: 1A, 1B, 1D, 2A, 2C, 3, 4 </li></ul><ul><li>Low levels are associated with depression and other psychiatric disorders. May be involved in migraine </li></ul>
  22. 23. <ul><li>histamine: </li></ul><ul><ul><li>present in pathways from hypothalamus to cortical areas & spinal cord </li></ul></ul><ul><ul><li>receptors: H1, H2, H3 (all present in brain) </li></ul></ul><ul><ul><li>functions related to arousal, sexual behaviour, drinking, pain </li></ul></ul><ul><li>Substance P </li></ul><ul><ul><li>found in primary nerve ending in the spinal cord </li></ul></ul><ul><ul><li>mediator of pain in the spinal cord </li></ul></ul>
  23. 24. NEUROPEPTIDES <ul><li>synthesized by ribosomes in the cell body </li></ul><ul><li>ER and Golgi apparatus enzymatically split the large molecule into smaller precursor or active molecules </li></ul><ul><li>Golgi apparatus makes vesicles </li></ul><ul><li>these vesicles are transported through the axoplasm slowly </li></ul><ul><li>remain in the terminal </li></ul><ul><li>release by a process similar to the other neurotransmitter </li></ul>
  24. 25. NEUROPEPTIDES <ul><li>however vesicle is autolysed and not reused </li></ul><ul><li>quantity of neuropeptides released is smaller than that of other neurotransmitters </li></ul><ul><li>but the neuropeptides are thousand times more potent </li></ul><ul><li>they also cause much more prolonged action </li></ul><ul><li>generally only one type of small molecule neurotransmitter is released by a neuron </li></ul><ul><li>several neuropeptides could be released </li></ul>
  25. 26. NEUROPEPTIDES <ul><li>Removal of neurotransmitter: </li></ul><ul><ul><ul><li>by diffusion into the surrounding fluids </li></ul></ul></ul><ul><ul><ul><li>enzymatic destruction (Ach) </li></ul></ul></ul><ul><ul><ul><li>active transport re-uptake into the presynaptic terminal </li></ul></ul></ul><ul><li>Actions </li></ul><ul><ul><li>prolonged closure of Ca pores </li></ul></ul><ul><ul><li>prolonged changes in cell metabolism </li></ul></ul><ul><ul><li>deactivation of specific genes </li></ul></ul><ul><ul><li>prolonged changes in excitatory or inhibitory receptors </li></ul></ul>
  26. 27. OPIOID PEPTIDES <ul><li> Endorphin </li></ul><ul><ul><li>present in pituitary, earliest discovered opioid peptide </li></ul></ul><ul><li>enkephalins: met-enkephalin, leu-enkephalin </li></ul><ul><ul><li>present at substantia gelatinosa in the spinal cord & brain stem reticular nuclei </li></ul></ul><ul><ul><li>widely distributed </li></ul></ul><ul><li>dynorphin </li></ul><ul><ul><li>recently discovered </li></ul></ul><ul><li>opioid peptides are involved in the descending pain inhibitory pathway </li></ul><ul><li>receptors:  ,  ,  </li></ul>
  27. 28. Other peptides present in the CNS <ul><ul><li>Substance P </li></ul></ul><ul><ul><li>ACTH </li></ul></ul><ul><ul><li>Oxytocin </li></ul></ul><ul><ul><li>Glucagon </li></ul></ul><ul><ul><li>Somatostatin </li></ul></ul><ul><ul><li>VIP </li></ul></ul><ul><ul><li>Prolactin </li></ul></ul><ul><ul><li>LH </li></ul></ul><ul><ul><li>TRH </li></ul></ul><ul><ul><li>Releasing hormones, </li></ul></ul><ul><ul><li>GH </li></ul></ul><ul><ul><li>Gastrin </li></ul></ul><ul><ul><li>CCK </li></ul></ul><ul><ul><li>Neurotensin </li></ul></ul><ul><ul><li>Insulin </li></ul></ul><ul><ul><li>Angiotesin II </li></ul></ul><ul><ul><li>Bradykinin </li></ul></ul><ul><ul><li>Calcitonin gene related peptide (CGRP) </li></ul></ul><ul><ul><li>Neuropeptide Y </li></ul></ul>
  28. 29. <ul><li>nitrous oxide (NO) </li></ul><ul><ul><li>present in brain </li></ul></ul><ul><ul><li>probably involved in memory </li></ul></ul>
  29. 30. Neuromodulators <ul><li>Neurotransmitters transmit an impulse from one neuron to another </li></ul><ul><li>Neuromodulator modulate regions or circuits of the brain </li></ul><ul><li>They affect a group of neurons, causing a modulation of that group </li></ul><ul><li>Neuromodulators alter neuronal activity by amplifying or dampening synaptic activity </li></ul><ul><ul><li>eg. dopamine, serotonin, acetylcholine, histamine, glutamate </li></ul></ul>
  30. 31. Neuromuscular junction
  31. 32. Neuromuscular junction <ul><li>This is a modified synapse </li></ul><ul><li>Consists of </li></ul><ul><ul><li>Presynaptic membrane (nerve terminal) </li></ul></ul><ul><ul><li>Synaptic cleft </li></ul></ul><ul><ul><li>Postsynaptic membrane (motor end plate) </li></ul></ul>
  32. 34. Presynaptic terminal (terminal knob, boutons, end-feet or synaptic knobs) <ul><ul><li>Terminal has synaptic vesicles and mitochondria </li></ul></ul><ul><ul><li>Mitochondria (ATP) are present inside the presynaptic terminal </li></ul></ul>Vesicles containing neurotransmitter (Ach)
  33. 35. Presynaptic terminal (terminal knob, boutons, end-feet or synaptic knobs) <ul><ul><li>Presynaptic membrane contain voltage-gated Ca channels </li></ul></ul><ul><ul><li>The quantity of neurotransmitter released is proportional to the number of Ca entering the terminal </li></ul></ul><ul><ul><li>Ca ions binds to the protein molecules on the inner surface of the synaptic membrane called release sites </li></ul></ul><ul><ul><li>Neurotransmitter binds to these sites and exocytosis occur </li></ul></ul>
  34. 36. Ca 2+ Ca 2+
  35. 37. Postsynaptic membrane (motor end plate) <ul><li>Postsynaptic membrane contain receptors for the neurotransmitter released </li></ul><ul><li>eg: Acetylcholine receptor </li></ul>Ach Na+ <ul><li>This receptor is Ach-gated Na+ channel </li></ul><ul><li>When Ach binds to this, Na+ channel opens up </li></ul><ul><li>Na+ influx occurs </li></ul>
  36. 38. <ul><li>Na+ influx causes depolarisation of the membrane </li></ul><ul><ul><li>End Plate Potential (EPP) </li></ul></ul><ul><ul><ul><li>This is a graded potential </li></ul></ul></ul><ul><ul><ul><li>Once this reaches the threshold level </li></ul></ul></ul><ul><ul><ul><li>AP is generated at the postsynaptic membrane </li></ul></ul></ul>
  37. 39. Ach release <ul><li>An average human end plate contains 15-40 million Ach receptors </li></ul><ul><li>Each nerve impulse release 60 Ach vesicles </li></ul><ul><li>Each vesicle contains about 10,000 molecules of Ach </li></ul><ul><li>Ach is released in quanta (small packets) </li></ul>
  38. 40. End plate potential <ul><li>Even at rest small quanta are released </li></ul><ul><li>Which creates a minute depolarising spike called Miniature End Plate Potential (MEPP) </li></ul><ul><li>When an impulse arrives at the NMJ quanta released are increased in several times causing EPP </li></ul>
  39. 41. Acetylcholinerase (AchE) <ul><li>After the Ach binding is over </li></ul><ul><li>Cholinesterase present in the synaptic cleft will hydrolyse Ach into choline and acetate </li></ul><ul><li>Choline is reuptaken to the presynaptic terminal </li></ul><ul><li>AchE is also found in RBC membranes </li></ul>
  40. 42. Axoplasmic transport <ul><li>A cellular process responsible for movement of mitochondria, lipids, synaptic vesicles, proteins, and other organelles to and from a neuron's cell body, through the axoplasm </li></ul><ul><li>anterograde transport </li></ul><ul><ul><li>movement toward the synapse is called </li></ul></ul><ul><li>retrograde transport </li></ul><ul><ul><li>Movement toward the cell body </li></ul></ul>
  41. 43. Smooth muscles <ul><li>NMJ not well developed </li></ul><ul><li>Smooth muscle does not depend on motor neurons to be stimulated </li></ul><ul><li>However, motor neurons (of the autonomic system) reach smooth muscle and can stimulate it — or relax it — depending on the neurotransmitter they release (e.g. noradrenaline or nitric oxide, NO)) </li></ul><ul><li>Smooth muscle can also be made to contract </li></ul><ul><ul><li>by other substances released in the vicinity (paracrine stimulation) </li></ul></ul><ul><ul><ul><li>Example: release of histamine causes contraction of the smooth muscle lining our air passages (triggering an attack of asthma) </li></ul></ul></ul><ul><ul><li>by hormones circulating in the blood </li></ul></ul><ul><ul><ul><li>Example: oxytocin reaching the uterus stimulates it to contract to begin childbirth. </li></ul></ul></ul><ul><li>The contraction of smooth muscle tends </li></ul><ul><li>to be slower than that of striated muscle </li></ul><ul><li>It also is often sustained for long periods </li></ul>

×