PSYC304 Lecture 04 - Neural Communication I PDF

PSYC304: Neural communication I (within cells) Jay Hosking, PhD 1  Overview A. Introduction to neural communication B. The resting membrane potential C. Postsynaptic potentials D. The action potential E. Conduction of the action potential...

PSYC304: Neural communication I (within cells) Jay Hosking, PhD 1  Overview A. Introduction to neural communication B. The resting membrane potential C. Postsynaptic potentials D. The action potential E. Conduction of the action potential 2  Learning objectives 1. What does it mean to say that neuronal communication is an electrochemical process? 2. Describe the chemical and electrical gradients for a neuron at rest. 3. What two proteins are responsible for the resting membrane potential? How so? 4. Describe how the resting membrane potential is established. 5. What two proteins are responsible for the action potential? How so? 6. Describe how an action potential occurs, including its threshold, stages, and refractory periods. 7. Why does conduction only happen in one direction along the axon? Can you imagine a possibility in which conduction could travel in the opposite direction? (This likely happens in nature.) 8. Describe the differences between conduction in unmyelinated versus myelinated axons. 9. Identify and define four key differences between postsynaptic potentials and action potentials. Additionally, describe where each occurs, and why. 3  Listen to Einstein(-ish) “Make things as simple as possible, but no simpler.” 4 Introduction  The synapse Site of neural communication 5 Introduction  So: How do all these cells communicate with one another? 6 Introduction  As a first step: How does communication occur within a single neuron? 7 Introduction A healthy neuron has a resting membrane potential (or membrane voltage) of between -60 and -80 mV (the voltage inside the neuron is 60-80 mV less than outside the neuron). extracellular electrode intracellular electrode (must have a very fine tip) 8 Resting membrane potential  The membrane potential Originally performed with invertebrates (why?) Varies a little from cell to cell / region to region (why?) https://www.youtube.com/ watch?v=k48jXzFGMc8 9 Resting membrane potential Neuronal communication is chemical 1. Primarily the result of two ions, sodium (Na+) and potassium (K+) 2. Ions move into or out of the cell, but not freely And yes, neurotransmission is also chemical, but we’ll talk about that one later! 10 Resting membrane potential Neuronal communication is electrical 1. Ions are positively and negatively charged (Na+ and K+ are both positive, as per “+”) 2. As they move into or out of cell, they change the potential (voltage) at the membrane Note: absence of pos. is neg.! i.e. remove a pos., leave a neg. 11 Resting membrane potential  Chemical gradients Ions want to flow from high concentration to low concentration 12 Resting membrane potential  Electrical gradients Charge/potential wants to flow from high concentration to low concentration, too Sometimes electrical and chemical gradients are at odds, causing an equilibrium that =/= 0mV 13 Resting membrane potential  The cell membrane - guardian Lipid bilayer is tightly packed, both hydrophobic and hydrophilic, keeping out all dangerous entities e.g.? 14 Resting membrane potential  Channels and pumps Only certain molecules and ions permitted via channels and pumps Channels: allow passive diffusion (i.e. along chemical gradient) Pumps: actively push ions against their chemical gradient Requires energy (ATP) channel pump 15 Resting membrane potential  A cell with no channels or pumps Nothing moves into or out of the cell 0mV K+ K+ Na+ K+ Na+ Na+ Na+ K+ K+ K+ Na+ K+ Na+ K+ Na+ Na+ Na+ Na+ K+ K+ K+ Na+ Na+ K+ 16 Resting membrane potential  The Sodium-Potassium Pump Embedded in cell membrane Extremely important Consumes 2/3rds of all neuronal energy! Pushes 3 Na+ out and 2 K+ in i.e. Active process that requires energy How does this affect the chemical gradients? How does this affect the electrical gradient? 17 Resting membrane potential  The Sodium-Potassium Pump 18 Resting membrane potential  Potassium “leak” channels K+ can move freely via K+ “leak” channels that are always open Na+ cannot move freely across the membrane It has channels, but they are usually closed 19 Resting membrane potential  Cells are polarized Na+/K+ pump pushing more Na+ out of cell than K+ into cell Result: inside of cell slightly more negative than outside But K+ can move freely through its leak channels Result: K+ wants to move with chemical gradient, out of the cell But this moving K+ is making the cell even more negative Result: flow of K+ stops when force of electrical gradient equals force of chemical gradient End result: cell has resting membrane potential of ~-70mV 20 Resting membrane potential  Cells are polarized Chemical force pushing K+ out of the cell equals Electrical force pushing K+ into the cell -70mV K+ K+ K+ K+ Na+ K+ Na+ Na+ K+ Na+ Na+ K+ Na+ Na+ K+ Na+ Na+ Na+ Na+/K+ pump (always working) K+ Na+ K+ K+ Na+ K+ K+ leak channel (always open) Na+ channel (closed) 21 Resting membrane potential  Cells are polarized 22 Resting membrane potential When a neurotransmitter molecule binds to a postsynaptic receptor, it can have one of two localized effects: 1. Depolarize the membrane (e.g., decrease membrane potential from -70 to -67mV) 2. Hyperpolarize the membrane (e.g., increase the membrane potential from -70 to -72mV) 23 Postsynaptic potentials When a neurotransmitter molecule binds to a postsynaptic receptor, it can have one of two localized effects: 1. Depolarize the membrane = Excitatory postsynaptic potential (EPSP) 2. Hyperpolarize the membrane = Inhibitory postsynaptic potential (IPSP) 24 Postsynaptic potentials When a neurotransmitter molecule binds to a postsynaptic receptor, it can have one of two localized effects: 1. Depolarize the membrane = EPSP = Increase likelihood that the postsynaptic neuron will fire an action potential (AP) 2. Hyperpolarize the membrane = IPSP = Decrease the likelihood that the postsynaptic neuron will fire an AP 25 Postsynaptic potentials When a neurotransmitter molecule binds to a postsynaptic receptor, it can have one of two localized effects: 1. Depolarize the membrane = EPSP = Increase likelihood that the postsynaptic neuron will fire an action potential (AP) 2. Hyperpolarize the membrane = IPSP = Decrease the likelihood that the postsynaptic neuron will fire an AP The transmission of postsynaptic potentials (PSPs) is graded, rapid, and decremental: PSPs travel like an electrical signal along an uninsulated wire. 26 Postsynaptic potentials  EPSPs and IPSPs sum both spatially and temporally 27 Postsynaptic potentials  AP Generation If the sum of the EPSPs and IPSPs that reaches the axon initial segment is sufficient to depolarize the membrane there above its threshold of excitation (e.g., -55mV) then an action potential (AP) is generated The AP is a massive momentary reversal of the membrane potential (e.g., from -70 to +55 mV) 28 The action potential  Reverse the polarity! Action potential: a rapid, brief reversal of the polarity at the membrane, from negative to positive It’s the main method of brain communication It’s all-or-none (off or on), not graded (e.g. 0-100%) i.e. always the same size/shape in a cell How do neurons convey magnitude, then? Why does this reversal happen? 29 The action potential  AP generation and conduction are both the result of voltage-activated ion channels (primarily Nav) 30 The action potential  Small depolarizations Remember: Na+ channels usually closed But these Na+ channels are voltage-gated, i.e. they open at a certain voltage (~-55mV) -70mV Na+ Na+ Na+ K+ K+ Na+ K+ Na+ K+ K+ K+ Na+/K+ pump (always working) Na+ Na+ Na+ K+ Na+ K+ Na+ K+ channel (always open) K+ K+ Na+ K+ Na+ Na+ Na+ channel (closed) 31 The action potential  Small depolarizations When enough EPSPs arrive at the same time (~5-10mV), the membrane is depolarized enough to reach the Na+ channels’ voltage threshold (threshold potential), and the channels open! Which direction does Na+ want to flow? Why? -70mV Na+ Na+ Na+ K+ K+ Na+ K+ Na+ K+ K+ K+ Na+/K+ pump (always working) Na+ Na+ Na+ K+ Na+ K+ Na+ K+ channel (always open) K+ K+ Na+ K+ Na+ Na+ Na+ channel (closed) 32 The action potential  Rapid huge depolarization Na+ channels open à Na+ into cell Effect? Cell membrane flips from neg. to pos. BUT Na+ channels have built-in inactivation gate Shut-off automatically, after ~1ms Na+ channels stay inactivated until membrane goes back to resting potential i.e. No more action potentials until reset! This leads to the absolute refractory period 33 The action potential  Repolarization K+ leak channels, as always, are open But even more K+ channels open during AP (these are voltage-gated, KV) Membrane is now pos., so which way does K+ flow? Effect: return cell to neg. resting membrane potential Slow closing of voltage-gated K+ channels leads to hyperpolarization phase and the relative refractory period Na+/K+ pump restores ion balance over time (slow) Pump has no effect on AP! 34 The action potential 35 The action potential Effect of subthreshold stimulation of an axon: An excitatory potential is produced, but it is not sufficient to elicit an AP 36 Conduction Effect of suprathreshold stimulation of an axon: An excitatory potential is produced that exceeds the threshold of excitation and produces an AP that continues undiminished down the axon 37 Conduction  Conduction in an Unmyelinated Axon Na+ channels are present all along the axon Unmyelinated axons: Na+ channels everywhere 38 Conduction  Axon Myelination 39 Conduction  Conduction in a Myelinated Axon Na+ channels are present all along the axon Unmyelinated axons: Na+ channels everywhere Myelinated axons: Na+ channels only at the Nodes of Ranvier 40 Conduction  Speed and direction Action potential is faster down myelinated axon than unmyelinated axon Why? (Two reasons) Action potential only travels in one direction Thanks to Na+ channel – why? 41 Conduction  End of the line Axon ends in terminal boutons (“buttons”) Bouton has vesicles (“bubbles”?) filled with neurotransmitters Action potential depolarizes bouton à Causes voltage-gated Ca++ channels to open à Ca++ causes SNARE complex to activate à SNARE complex fuses the vesicles with membrane à Neurotransmitters released into synapse 42 Neurotransmission  End of the line Axon ends in terminal boutons (“buttons”) Bouton has vesicles (“bubbles”?) filled with neurotransmitters Action potential depolarizes bouton à Causes voltage-gated Ca++ channels to open à Ca++ causes SNARE complex to activate à SNARE complex fuses the vesicles with membrane à Neurotransmitters released into synapse Danko Dimchev Georgiev, M.D. 43 Neurotransmission  Welcome to the synapse Dendrite membrane has special receptors that fit, like lock and key, with the neurotransmitters Receptors are often just (closed) channels that open when they bind with neurotransmitter! i.e. ligand-gated ion channels 44 Glu: glutamate, most common excitatory neurotransmitter Neurotransmission  Types of Potentials PSPs APs Graded Yes No Strength AM FM Rapid Yes Less so Decremental Yes No 45  A virtual neuron 1. Go to: https://phet.colorado.edu/en/simulation/neuron and run the simulation 2. Identify three proteins that we discussed 3. Identify one protein we did not discuss—it is real, but not particularly physiologically relevant for our story of RMPs and APs 4. Describe what’s happening at rest (i.e. during resting membrane potential), as regards ionic flow (it helps to zoom in) 5. Describe the order of events when you stimulate the neuron (it helps to slow it down) 6. Turn on the potential chart (bottom right corner). What do you see when you stimulate the neuron? Be specific about voltage changes. 7. Turn on the “Show Concentrations” option (bottom right corner). What do the concentrations tell you at rest? How do those concentrations change when you stimulate the neuron? What do those changes tell you about the effects of an action potential? 46 Totally optional extra learning