Lecture 8: Synaptic Transmission - PDF

Depolarization Rising Phase of AP AP depends on ion currents & voltage- gated channels channels Na+v = voltage gated sodium channel Fig 42.8 At t=0 Na+v & K+v Na+v channel opens Na+v channel closes K+v = voltage...

Depolarization Rising Phase of AP AP depends on ion currents & voltage- gated channels channels Na+v = voltage gated sodium channel Fig 42.8 At t=0 Na+v & K+v Na+v channel opens Na+v channel closes K+v = voltage gated Channels closed (EP). Na+ flows in. and inactivates. potassium channel Stimulus opens them. depolarization depolarized peak depolarization NOTE: K+ leak channels are always open. 1 The Rest of the AP Falling Phase of AP AP depends on ion currents & voltage- gated channels Fig 42.8 K+v channel opens K+v channel still K+v channel closes K+ flows out. open at RMP Na+v still inactivated K+ still flows out hyperpolarization repolarization (briefly) Na+/K+ pump returns RMP concentration gradient Refractory period NOTE: K+ leak channels are always open. 2 The Hodgkin-Huxley Cycle AP rise phase is Positive Feedback Initial depolarization Further Opening of Na+v membrane channels increases depolarization permeability to Na+ Increased Na+ flow 3 AP Propagation Along Axon AP initiated in axon hillock (concentration of Na+v Conducted unchanged along axon membrane channels) to terminals Dendrites & cell body – concentration of K+v channels reduces backpropagation into soma 4 Propagation of Action Potential Action potentials move along an axon as the ion flows generated in one segment depolarize the potential in the next segment. Will look at this for both Unmyelinated axons and Myelinated axons AP Conduction in UNMYELINATED Axon Fig 42.9 Reduced threshold at axon hillock (spike initiating zone) Concentration of Na+v channels Current spreads along membrane toward terminals (new AP) 6 AP Conduction in UNMYELINATED Axon Fig 42.9 Adjacent (downstream) Na+v channels reach threshold - from large depolarization (new AP) Refractory period prevents backpropagation 7 AP Conduction in UNMYELINATED Axon Fig 42.9 Next adjacent (downstream) Na+v channels reach threshold etc. Axon diameter determines speed of conduction (larger = faster) – up to 40 m/s Typical of most invertebrates 8 Saltatory Conduction In myelinated axons, ions can flow across the plasma membrane only at nodes where the myelin sheath is interrupted. Action potentials skip rapidly from node to node. Saltatory conduction allows thousands to millions of fast- transmitting axons to be packed into a relatively small diameter. AP Conduction in MYELINATED Axon Fig 42.10 Myelin (protein and lipid) insulation prevents ions from crossing the membrane – reduces current loss Concentration of Na+v and K+v at nodes – allows ions to cross membrane 10 AP Conduction in MYELINATED Axon Fig 42.10 11 AP Conduction in MYELINATED Axon Fig 42.10 Axon hillock similar to unmyelinated neuron Similar conduction process but current spreads quickly between nodes 12 AP Conduction in MYELINATED Axon Fig 42.10 Saltatory (jumping) conduction from node to node to reach terminals Higher conduction velocities (up to 100 m/s) – Vertebrates 13  Biol 224.3 – Animal Body Systems Lecture 8: Synaptic Transmission Dr Joan Forder Supplementary Reading: Textbook (5th Edition, Chapter 42, page 1134-1138 ) 14 Where we are headed Synapses: pre vs post synaptic Electrical synapses Chemical synapses Neurotransmitters Neurotransmitter receptor types Electrophysiology Graded Potentials - PSPs: EPSPs & IPSPs Summation Evolution of the Nervous System Divisions of the Nervous System  Synapses Site where a neuron communicates with another neuron or effector Presynaptic cell Neuron that sends a signal Postsynaptic cell Neuron that receives a signal https://media.istockphoto.com/id/1366769735/photo/synaptic- transmission.jpg?s=612x612&w=0&k=20&c=PuvvMkTuLec7P7A4sPG--ure1ruwXm5sYuSbYRQqLQc= Two Types of Synapses Electrical synapse Impulses (ions) pass directly from presynaptic cell to postsynaptic cell Examples: cardiac muscle cells; neurons in a few invertebrate animals Chemical synapse Neurotransmitter (chemical) released by presynaptic cell diffuses across synaptic cleft Binds to receptors in the plasma membrane of postsynaptic cell Examples: majority of neurons  Electrical synapses Presynaptic AP carries on as postsynaptic AP Gap junctions directly connect cytoplasm of each cell. Ions flow between cells Rapid flow of current Synchronous activity – escape responses Cannot be modulated excitatory only Fig 42.11 18 Chemical Synapse Pre and Postsynaptic neurons separated by synaptic cleft Neurotransmitter is stored in vesicles within the axon terminals of Presynaptic neuron Fig. 42.12, p. 1135  Vesicles Release Neurotransmitter AP cause Ca2+ influx through voltage- gated Ca2+ channels Ca2+ causes vesicles to move to the plasma membrane, fuse, and release neurotransmitter into the cleft Fig 42.12 20  Postsynaptic Binding Neurotransmitter binds to postsynaptic receptors – channels open – depolarization (excitatory) or hyperpolarization (inhibitory) Fig 42.12 Allows for integration of multiple presynaptic inputs (up to 1,000) Summed postsynaptic excitation or inhibition 21 Experimental Research: Demonstration of Chemical Transmission of Nerve Impulses Heart 1 is connected to the Fig. 42.13, p. 1136 vagus nerve Stimulated Heart two is not connected to the vagus nerve Receives solution from Heart 1 Heart 2 shows same (but delayed) reaction Conclusion: Heart 2 must have received something in the solution from Heart 1 that make it react as if it was stimulated by the vagus nerve. Neurotransmitters Work in Two Ways Some neurotransmitters bind directly to ligand-gated ion channels in the postsynaptic membrane. Binding opens or closes the channel gate Examples: Na+, K+, and Cl- Others work more slowly, acting as first messengers, binding to G-protein–coupled receptors in postsynaptic membrane. Triggers second messenger (leads to opening or closing of gated channel) Review: Neurotransmitter Release Neurotransmitters are released from synaptic vesicles into the synaptic cleft by exocytosis. Exocytosis Triggered by entry of Ca2+ ions into cytoplasm of axon terminal (through voltage-gated Ca2+ channels opened by arrival of action potential) Neurotransmitter release stops when action potentials cease arriving at axon terminal. Neurotransmitters removed from synaptic cleft Broken down by enzymes Taken up by axon terminal or glial cells Neurotransmitters Many different kinds Diverse effects All bind to a receptor protein in post- synaptic membrane Each neurotransmitter has several different receptors and thus Can stimulate or inhibit an effector cell (depending on the receptors present) 25 e.g. Acetylcholine Stimulates skeletal muscle contraction acts via a nicotinic receptor Inhibits cardiac muscle contraction acts via a muscarinic receptor 26 Two Classes of Acetylcholine Receptor Proteins Ionotropic receptors Ligand-gated ion channels Post-synaptic response depends on ion current e.g. Nicotinic receptor is a Na+ channel The binding of two acetylcholine molecules opens the ion channel permitting ions to flow through the membrane Causes depolarization Metabotropic receptors Influences post-synaptic cell indirectly Post-synaptic response depends on ion current e.g. muscarinic receptor Connects to a G-protein 27 Metabotropic receptors acts via an intracellular signal (2nd messenger) complex cell biochemistry Wide diversity of effects on cells 28