1 / 35

Synaptic transmission

Synaptic transmission. Module 725 Lecture 2. Aim. Why do we need synapses? To know about chemical synapses diversity flexibility mechanisms. Overview. Neurotransmitters Synaptic structure Transmitter release Transmitter breakdown/uptake Ionotropic receptors. Neurotransmitters.

shadow
Download Presentation

Synaptic transmission

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Synaptic transmission Module 725 Lecture 2

  2. Aim • Why do we need synapses? • To know about chemical synapses • diversity • flexibility • mechanisms

  3. Overview • Neurotransmitters • Synaptic structure • Transmitter release • Transmitter breakdown/uptake • Ionotropic receptors

  4. Neurotransmitters • Acetylcholine • amino-acids • glutamate • GABA • peptides • FMRFamide • NO (see next week)

  5. Synaptic structure • Neuromuscular junction • CNS synapses • Common features • transmitter stored in vesicles • receptors on post-synaptic membrane • cell-cell signalling to organise synapse

  6. Neuromuscular junction

  7. CNS synapses

  8. Overview of physiology • Simulation athttp://lessons.harveyproject.org/development/nervous_system/cell_neuro/synapses/release.html

  9. Transmitter release • calcium-dependent • vesicle cycling - or kiss and run

  10. Calcium domains • squid giant synapse • use n-aequorin-J as Ca indicator

  11. Calcium-dependency • Calcium entry very near vesicle! • micro or even nano-domains • synaptotagmin as Ca sensor ?

  12. Vesicle cycling • Conventional view • need recycling because no evidence of increase in membrane area • e.g. capacitance measurements

  13. Vesicle proteins • synaptobrevin & SNAP-25 anchor vesicle membrane to plasma membrane • syntaxin helps in conformational change • synaptotagmin as Ca sensor

  14. Synaptotagmin • calcium sensor • arginine in C2A and C2B domains

  15. Exocytosis • free energy barriers need to be overcome during fusion

  16. Endocytosis • Clathrin coats “empty” vesicles Movie from http://www.hms.harvard.edu/news/clathrin/

  17. Kiss and run

  18. testing… testing... • capacitance measurements- measures surface area • GFP-derivative called synaptophlorin reports pH (vesicles very acid) • FM dye which fluoresces only in membrane

  19. Summary so far • transmitter put into vesicles • vesicle release is Ca-dependent • major protein players include • synaptotagmin • SNARE • clathrin

  20. Breakdown or uptake? • esterase (ACh, peptides) • transport - mostly into glia (amino acids)

  21. Re-uptake • 12 membrane spanning regions • co-transport using Na gradient

  22. Uptake inhibitors • major drugs • cocaine - block serotonin & dopamine reuptake • Prozac - selective serotonin reuptake inhibitors serotonin cocaine prozac

  23. Summary so far • transmitter put into vesicles • vesicle release is Ca-dependent • transmitter recycled • after breakdown • direct pump for reuptake

  24. Ionotropic receptors • Ionotropic receptors have an integral channel which opens when receptor binds • Metabotropic receptors activate a second messenger internally • Important ionotropic receptors include • nicotinic ACH receptor • glutamate (NMDA, AMPA, Kainate) • GABA

  25. Nicotinic ACh receptor • 2 a, one each of b,g , d • ACh binds to a - need 2 ACh to open channel

  26. Nicotinic ACh receptor • highly conserved residues binding ACh

  27. Glutamate receptor • 2 a, one each of b,g , d • glu binds to a - need 2 glu to open channel • NMDA receptors alsoneed glycine

  28. Multiple glu receptors • Named after agonists

  29. NMDA receptors (I) • blocked by Mg, except at depolarised voltages • need glycine as cofactor squirt a-a and see cell current

  30. NMDA receptors (II) • may provide slow component to synapse stimulate presynapticneuron and see cell current

  31. AMPA & Kainate receptors • May both be used at same synapse • stimulate presynaptic cell and record voltage • APV blocks NMDA, GYKI blocks AMPA LY293558 blocks kainate

  32. GABAA receptor

  33. Benzodiazepines e.g. Valium (=diazepam) hypnotic, anxiolytic, anticonvulsant, myorelaxant and amnesic Barbiturates e.g. pentobarbital sedative action GABAA - drug action

  34. GABAA - diazepam • longer openings in bursts control DZ

  35. Summary • transmitter put into vesicles • vesicle release is Ca-dependent • transmitter recycled • after breakdown • direct pump for reuptake • ionotropic receptors • great diversity • homologous subunits • Synaptic transmission major drug target

More Related