Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
List of types of proteins wikipedia , lookup
Index of biochemistry articles wikipedia , lookup
Membrane potential wikipedia , lookup
Endomembrane system wikipedia , lookup
Action potential wikipedia , lookup
SNARE (protein) wikipedia , lookup
G protein–coupled receptor wikipedia , lookup
NMDA receptor wikipedia , lookup
Signal transduction wikipedia , lookup
Clinical neurochemistry wikipedia , lookup
Endocannabinoid system wikipedia , lookup
Lecture 2 Synapses Neuron-cell communication http://biolpc22.york.ac.uk/632/nervelectures.html Aim to know: mechanism of synaptic action drugs which interfere with synaptic action diseases of synapses Reading Matter Book Nicholls DG (1994) Proteins Transmitters and Synapses. Blackwell Papers: Jessell TM, Kandel ER (1993) Synaptic transmission - a bidirectional and self-modifiable form of cell-cell communication Cell 72S 1-30 Whittaker, V. (1990) The contribution of drugs and toxins to understanding of cholinergic function Trends Pharm Science 11: 8-13 (in the photocopy collection) Revision Neurons have channels voltage gated ligand gated Resting and action potentials depend on voltage gated channels Connections between neurons usually called synapses Electrical connections Membrane resistance too high for direct current flow from cell to cell Na + gap junction pre-synaptic post-synaptic Chemical connections release chemical transmitter respond with receptors advantages effective excite or inhibit variable gain disadvantages slower than electrical [??] Examples of synaptic connections Examples from snail neurons Excitation Inhibition Schematic diagram neuromuscular junction Freeze fracture resting stimulated Quantal release Miniature EPSP time traces EPSP - excitatory post-synaptic potential Stimulated EPSP overlaid traces Ca++ needed for release Ca++ dye in presynaptic neuron [Ca] rises at end of action potential Ca++ block stops synapse presynaptic Vm (voltage clamp) presynaptic I Ca++ postsynaptic Vm Ca++ block stops synapse presynaptic EGTA blocks transmission control EGTA Vesicle fusion cycling fusion Vesicle cycling? fusion hypothesis kiss & run clathrin coating kiss & run Synaptic Toxins tetanus & botulinum toxins blocks transmitter release interacts with (vesicle/membrane proteins) produced by Clostridium bacteria ACh cycling ACh pumped into vesicle ACh esterase Summary so far transmitter is stored in vesicles vesicles released calcium influx nearby calcium influx triggered by depolarisation from action potential Pharmacology of receptors many kinds of receptors ACh glutamate, glycine serotonin, dopamine peptides, FMRFamide separate pharmacologically each receptor binds its own unique profile of drugs Pharmacology of receptors Nicotinic ACh receptor agonist - nicotine, succinylcholine antagonist - curare, bungarotoxin Muscarinic ACh receptor agonist - muscarine antagonist - atropine Ionotropic & Metabotropic Ionotropic receptor binding opens hole ions flow through metabotropic receptor binding activates G-protein requires second messenger 7 transmembrane format phosphorylates another protein [channel] Second messengers make synapses slow cAMP IP3/DAG/PKC arachidonic acid = = norepinephrine How does 5-HT act? apply 5-HT to cell patch elsewhere Effect of 5-HT 5-HT could block a channel reduce chance of opening increase chance of closing reduce current 5-HT = = serotonin Effect of 5-HT 5-HT closes K+ channels channel size the same reduced chance of opening Summary so far transmitter is stored in vesicles vesicles released calcium influx nearby calcium influx triggered by depolarisation from action potential multiple kinds of receptor ionotropic / metabotropic different transmitters Excitation and inhibition spatial summation temporal summation Reversal of IPSPs Inhibitory postsynaptic potentials reverse at -70 (K+) or -50mV (Cl-) Pre- & Post- synaptic inhibition Post-synaptic inhibition leads to summation of excitatory and inhibitory transmitter Pre-synaptic inhibition occurs between two axons it prevents release of transmitter Diagram of synaptic layout exc itation postsynaptic inhibition presynaptic inhibition Diagram of synaptic response Transmitters & disease myasthenia gravis autoimmune response to ACh receptor Parkinson’s disease loss of dopaminergic neurons Confusing points to watch out for Note the difference between inhibition and antagonism pre- and postsynaptic inhibition conduction and conductance Summary to end transmitter is stored in vesicles vesicles released calcium influx nearby calcium influx triggered by depolarisation from action potential multiple kinds of receptor ionotropic / metabotropic fast/slow different transmitters excitatory / inhibitory