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Unformatted text preview: PSL302Y: Lecture 12, by Prof. MacKay! Ionotropic effects Fri., Oct. 8, 2010 Synaptic Potentials Ionotropic effects Ligand binding opens an ion channel Ionotropic effects ion channel ma be specific for may - Ligand binding opens Ligand binding + an ion channel + opens an ion channel 1 mV cations (Na (Na+, - Ion channel may be specific for cations , K ) K+) EPSP (excitatory post-synaptic -> EPSP (depolarizing) may potential), depolarizing ion channel ma be specific for 1 mV - Size of depolarization is small: tiny patch ofEPSP (Na+, + cationschannelare)opened; influx for Clor ionchannels Kmay be specific membrane where cation (depolarizing) of cations at low conc + ion or K IPSP (hyperpolarizing) ( yp p g) - Or ion channel may be specific for Cl- or K+ ion -> IPSP or ion channel may20-40 ms for Cl- 20 ms duration of PSP is be specific (Inhibitory post-synaptic potential), hyperpolarizing or K+ ion IPSP (hyperpolarizing) ( yp p g) (increase -vity inside membrane) determines effect, not receptor 20 ms - Duration of PSP: 20-40 ms duration of PSP is 20-40 ms transmitter - Receptor determines effect, not transmitter receptor determines effect, not transmitter
Synaptic Potential: Electrochemical Transmission
October 8, 2010 - Acetylcholine binds to nicotinic receptors on plasma membrane = cause cation channels to open
Synaptic Potentials Spread of PSPs PSPs are are generated inexcitable membrane - PSPs generated in and cell bodies in inexcitable membrane of neuronal dendrites (extensions of of neuronal dendrites Dendritic Spines neurons) and cell bodies nearest excitable membrane is initial segment of axon - Nearest excitabletomembrane is initial segment of axon (PSPs here are tiny = useless!) p ss ve co duc o of S s passive conduction o PSPs o initial spines segment where they must summate - Passive conductiontoof PSPs to initial segment where they must summate to depolarize depolarize membrane to threshold levels membrane to threshold levels
Synaptic Potentials Spread of PSPs October 8, 2010 October 8, 2010 Dendritic Spines Dendritic Spines - Spines isolate individual synaptic inputs so that they can be 2 Spines isolate individual synaptic inputs so that they can be independently modified in learning modified in learning situations independentlysituations. spines -EPSPs must travel thru cell body to initial segment (where potential can be conducted down axon) -BUT it must make it past the IPSP, which if activated, inhibits EPSPs (the depolarizing current) -IPSP has strategic position btwn EPSP and initial segment
Spines isolate individual synaptic inputs so that they can be independently modified in learning situations. 3 3 1 of 4 1) Spatial summation: minimum of 10 30 10-30 synchronous EPSPs in dendritic tree, each PSL302Y: Lecture different synapse generated at a 12, by Prof. MacKay! Fri., Oct. 8, 2010 2) Temporal summation: only a few active synapses, but each generating EPSPs at high Types of PSP summation frequency; summated potentials reach 1) Spatial summation: min of 10-30 synchronous EPSPs in dendritic tree, each threshold over a period of time generated at a diff synapse - Arrive at the initial segment at the same time and build off each other Synaptic Potentials 2) Temporal summation: only a few active synapses, but each generating EPSPs at high freqcy; summated potentials reach threshold over a period of time - Allows EPSPs to build off the tails of previous EPSPs at the initial segment October 8, 2010 Synaptic Potentials October 8, 2010 - There are certain areas in the body where certain types of summation are not allowed; i.e. Temporal summation not permitted in auditory system, or you wouldn't know when Generating a `spike' train you heard something 4 When summated PSPs achieve threshold, an threshold a.p. (spike) is triggered Electrotonic distance Electrotonic distance above threshold, if summated PSPs remain - Synapses on dendritic tree are usually w/i 0.4 of axonal initial segment by continued spike this should be signalled - On avg, >50% EPSP amplitude reaches the initial segmentare usually within generation synapses on dendritic tree BUT holding membrane potential - IPSPs have strategic advantage: located close toof axonal initial segment initial segment -> can shunt above 0.4 threshold causes depolarization block depolarizing EPSP currents out of cell on average, more than 50% of EPSP - One of the most important mechs that amplitude reaches the initial segment regulate signaling in the nervous system (lots of excitation happening; inhibitionIPSPs have strategic advantage: located regulates which excitatory signals pass) S g g Generating a `spike' train - When summated PSPs achieve threshold, an a.p. (spike) is triggered - If summated PSPs remain above threshold, this should be signalled by continued spike generation - BUT holding membrane potential above threshold causes depolarization block close to initial segment can shunt depolarizing EPSP currents out of cell 5 Afterhyperpolarization - Voltage-gated K+ channels at initial segment cause afterhyperpolarizations - Hyperpolarization after each spike ensures that Na+ channels reconfigure, and membrane excitability is restored 6 2 of 4 PSL302Y: Lecture 12, by Prof. MacKay! Pre-synaptic inhibition 8, 2010 Fri., Oct. Substrate is axo-axonic synapse axo axonic release of GABA onto bouton opens GABA-gated Cl- channels depolarizing currents in bouton cause influx of Cl-, which restores resting potential C gp prevents opening of voltage-gated Ca++ channels and exocytosis of vesicles Ligands for Ionotropic Receptors Acetylcholine (ACh) -- nicotinic receptor Glutamate GABA Glycine Serotonin -- 5-HT3 ATP -- P2X Pre-Synaptic Inhibition - Substrate is axo-axonic synapse - Release of GABA onto bouton opens GABA-gated Ch- channels - Depolarizing currents in bouton cause influx of Cl-, which restores resting potential - Prevents opening of voltage-gated Ca++ channels & exocytosis of vesicles Metabotropic Effects - Ligand-receptor binding activates an enzyme (usually via G-protein coupling) - [2nd messenger] or - 2nd messenger is cAMP, cGMP, or InP3 - 2nd messenger activates other enzymes, e.g. Phosphokinases which phosphokinase which phosphorylate ionotropic receptors -> modulate ion currents -adrenoceptor - Binding of NA to -receptor activates adenyly cyclase via G-protein alteration - [cAMP] (2nd messenger) - cAMP activates kinases which phosphorylate membrane Ca++ channel - Ca++ influx (important for heart muscle) Ligands for Metabotropic Receptors ACh -- muscarinic receptors Peptides: substance P, -endorphin, ADH Catecholamines: noradrenaline, dopamine Serotonin Glutamate -- mGluR GABA -- GABAB receptors Purines: adenosine, ATP Free radials: NO, CO 8 3 of 4 Synaptic Potentials October 8, 2010 PSL302Y: Lecture 12, by Prof. MacKay! Fri., Oct. 8, 2010 Gaseous Transmitters - NO, CO and H2S are volatile gases used as neurotransmitters - Cannot be stored in vesicles -> synthesized 2010 on Synaptic Potentials October 8, demand - Synthesis triggered by Ca++ influx into cell - E.g. NO synthase is activated Ca++ and catalyzes NO production from L-arg Transmitter removal NO receptor transmitter is catabolized by an enzyme - NO1)diffuses into all nearbyenzyme, cells e.g. acetylcholinesterase breaks down ACh - Binds to haemtransported into pre- or in guanylyl cyclase -> activates enzyme to produce cGMP (2nd 2) transmitter is messenger) neurones or into astrocytes, post-synaptic e.g. modulates other enzymes - cGMPglutamate transporter molecule couples or affects ion channels; e.g. gK+ NO receptor in vascular glu absorption with Na+ diffusion into cells smooth muscle -> vasodilation NO diffuses into all nearby cells binds to haem in guanylyl cyclase Transmitter removal activates enzyme to produce cGMP (2nd 1) Transmitter is catabolized by enzyme, e.g. Acetylcholinesterase breaks down ACh messenger) 2) Transmitter is transported into pre- or post-synaptic neurones or intoother enzymes or affects astrocytes, e.g. G y cGMP modulates Glutamate transporter molecule couple glu absorption w/ Na+ diffusion+ into cellssmooth ion channels; e.g. gK in vascular muscle vasodilation 11 12 4 of 4 ...
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This note was uploaded on 03/27/2012 for the course PSL PSL300 taught by Professor Mackayfrench during the Fall '11 term at University of Toronto- Toronto.
- Fall '11