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Announcements • Mid term room assignments posted to webpage Lecture 01 A – Ho S361 (Pavilion) Hoang – Lischka S309 Lishingham - Ngui S143 Nguyen – Seguin S128 Sek – Zia H305 Lecture 02 S319 A. Excitor B. Inhibitor Record voltage Simple case: Threshold A B Vm Depolarizing excitatory EPSP Threshold A+B=smaller Vm hyperpolarizing inhibitory IPSP How to get hyperpolarizing potential? • Neurotransmitter receptor is permeable to an ion whose Eion is more negative than resting membrane potential • usually Cl- or K+ Hyperpolarizing Synaptic Potential +60 mV 0 mV + + K+ -80 mV More complex case: Threshold A B Vm Why??? Depolarizing excitatory Threshold A+B=smaller Vm Depolarizing inhibitory Reversal Potential • Membrane potential at which there is no net synaptic current Measuring Reversal Potential eg. Frog NMJ Current source +25 stimulus Control resting membrane potential 0 Reversal potential -50 -100 Stimulate nerve Record membrane potential • Many neurotransmitter receptors are permeable to more than one ion – Non-selective • The reversal potential depends on the equilibrium potential and permeability of each ion – It will usually be between the equilibrium potential of the permeable ions eg. Acetylcholine channel • Permeable to both K+ and Na+ • For Frog muscle: • EK = -90 mV • ENa = +60 mV Neurotransmitter receptor ENa = +60 mV K+ VmENa +25 0 Reversal potential Vm=Erev -50 Erev>Vm>EK -90 EK = -90 mV VmEK Na+ How can depolarizing potential be inhibitory? • Excitatory synapses have a reversal potential more positive than threshold • Inhibitory synapses have a reversal potential more negative than threshold How can depolarizing potential be inhibitory? Erev Threshold Erev A B Vm Example: Cl- permeable receptor in a cell whose Vthresh >ECl- > Vm Inhibition • Channels of inhibitory synapses ‘shortcircuit’ excitatory synapses • Because neurotransmitter channels will drive the membrane potential toward their reversal potential • Neurotransmitters and receptors • Synaptic Integration Types of Receptors 1. Ligand-gated ion channels • • • Neurotransmitter binding to receptor opens an ion channel Directly changes the membrane potential of the postsynaptic cell Also known as ‘fast’ synaptic transmission 2. G-Protein Coupled Receptors • • • Transmitter binds to receptor which activates intracellular molecules Can directly or indirectly change the membrane potential Also known as ‘slow’ synaptic transmission Neurotransmitter Receptors Ligand-gated ion channels Acetylcholine Excitatory (Nicotinic) Glutamate Excitatory (AMPA, NMDA) Serotonin Excitatory (5-HT3) GABAA Inhibitory Glycine Inhibitory Neurotransmitter Receptors G-Protein coupled receptors (muscarinic) Usually excitatory Glutamate Variable effects Acetylcholine (metabotropic) Serotonin Variable effects (5-HT1-7) GABAB inhibitory Same neurotransmitter, different receptors G-protein coupled receptor receptor direct effect G-proteins Open or close ion channel indirect effect GDP GTP Activate intracellular molecules Regulate other cellular functions eg gene expression What happens to neurotransmitter after it is secreted? • Acetylcholine – Broken down by Acetylcholinesterase into Choline and Acetate – Choline transported back into nerve terminal and resynthesized into Acetylcholine • Glutamate – Transported into glia or the nerve terminal and converted to glutamine • Serotonin – A neurotransmitter used in the emotional centres of the brain – Prozac is a drug that inhibits the reuptake of serotonin – Therefore, Prozac makes serotonin remain in synaptic cleft longer Synaptic Integration The sum of all excitatory and inhibitory inputs to a cell. 1. Spatial Summation 2. Temporal Summation Spatial Summation • The addition of several inputs onto one cell A B A B A+B A B A+B Temporal Summation Stim once A Stim twice Stim twice Synaptic Integration Summation Synaptic inputs Soma and dendrites Axon Hillock Passive current flow Above threshold? Yes Action Potential Conducts down axon No Passive Current Decays to zero Summary • Excitation and inhibition in relation to the reversal potential • Fate of neurotransmitters after release • Types of transmitters and their receptors • Synaptic integration leading to action potentials
