In Class Questions for Action Potential tutorial 2022-09-13.ppt

Action Potential Tutorial Dr. Harry Witchel Questions or comments? Contact: [email protected] 1 SET UP TABLES FOR CLASS GROUP WORK Front of Class: Screen Table Table 2 Purpose of Session • To allow students to work out answers with each other via discussion Recommended approach Work out...

Action Potential Tutorial Dr. Harry Witchel Questions or comments? Contact: [email protected] 1 SET UP TABLES FOR CLASS GROUP WORK Front of Class: Screen Table Table 2 Purpose of Session • To allow students to work out answers with each other via discussion Recommended approach Work out individually or in small groups Answer as a plenary class 3 Ions and Electric Potentials 4 What voltage is the resting membrane potential (RMP) and why does the cell membrane “rest” at that voltage? • The resting membrane potential is -70 mV *E • The reason the inside of the membrane is negative at rest (ie the inside is negative with respect to the extracellular space) is because K+ is always slowly leaking out; this leaves behind unbalanced negative Click to see answer anions. • The RMP is close to the equilibrium potential of K+ (EK = -90 mV) because (of all ions) the membrane is most permeable to K+ 5 Draw a graph of a neural action potential. Include axes (and their labels), units, and approximate numerical values. RISATIO DEP OLA RISA T ION OVERSHOOT A REPOL N • AP should last 2-4 ms. RMP should be between -85 mV and -55 mV. The AHP should go negative to the RMP, but it should remain slightly above -90 answer mV (EK). Overshoot Click to see THRESHOLD should peak between 0 and +40 mV. RESTING STATE Hyperpolarization 6 For each of those phases of the action potential: list the ionic current (and the ion’s direction of movement) that is responsible. • Resting membrane potential is determined primarily by K+ moving down its concentration gradient (leaking out of cell), leaving behind negative anions inside membrane. The K+ is leaking out. • Depolarisation is due to Na+ rapidly coming into the cell. • The threshold is the voltage above which the cell is committed to completing an action potential. • – It occurs when the amount of inward Na+ current depolarizing the cell becomes more than the outward K+ current repolarising the cell back to the RMP. see answer Repolarisation is due toClick Na+tochannels inactivating. Also K+ is rapidly leaving the cell via the delayed rectifier channels. – It is NOT the Na/K pump, which only changes Vm by 3 mV. • The afterhyperpolarisation is when Vm is most close to EK at the end of the AP. Many different sources of K+ permeability cause K+ to flow out: inward rectifiers, leak, and delayed rectifiers (which are delayed in their closing). In addition, during the AHP the amount of Na+ flowing becomes miniscule because the Na+ channels are inactivated (which occurs after a delay when Vm is above -40 mV). 7 What is a graded potential? • It is a change in the membrane potential that can vary in voltage amplitude and in time duration. – A graded potential is not amplified, and it is not all-or-none. It varies more than an AP. • It occurs at receptor cells (eg rods and cones). It is important in transduction of light/pressure into a graded Click to see answer electrical potential • Also occurs at synapses. – If graded potential is large – It can trigger an AP in the – Post-synaptic cell http://youtu.be/N4Z_Bl337BQ Graded potential Action potential 8 What is a refractory period? • A refractory period is a time duration after one action potential has just fired when another action potential either cannot be restimulated (absolute refractory period) OR is resistant to restimulation (relative refractory period) to begin a new action potential. It Click to see answer often is associated with Vm being lower than the RMP (i.e. the after-hyperpolarisation), and it is usually caused by a high permeability to K+ (i.e. more K+ channels are open than at rest). 9 What is an equilibrium potential? • It is the voltage where the amount of a particular ion (e.g. Na+) flowing out of the cell = the amount of that ion flowing in. It happens when the electrochemical forces for that ion type are in equilibrium. Click to see answer • E.g. For Na+, this occurs when the diffusion (chemical) forces pushing Na+ into the cell equal the voltage (electrical) forces pushing Na+ out of the cell 10 Name the equilibrium potentials for Na+, K+, Ca2+ and Cl¯ (in a typical cell). • • • • ENa = ~ +55 mV (or you could say +60). EK = ~ -90 mV ECa = ~ +123 mV Click to see answer ECl = ~ -40mV (although this varies by cell type and is sometimes quoted as being -65 mV) 11 EK = -90 mV ENa = +55 mV Electrical Force + - - - - - + - - - - K+ K+ _ + + + _ + + + + + _ _ _ + + K+ 90 _ + Net Net 0 mV Force 0 mV Force Na+ Na+ Na+ Na+ Na+ Na+ mV K+ Chemical Force (diffusional) Na+ Na+ Na+ Convention: a force is positive if it drives positive ions outward V 5m -5 K+ _ + - K+ K+ _ + K+ K+ + _ _ +55 mV -90 mV + + + + Electrical Force Na+ Na+ Na+ Chemical Force (diffusional) 12 ECa = +123 mV ECl = -65 mV _ + + _ Electrical Force _ + + + + _ + _ + + + + + _ + + - - - -65 mV _ _ _ _ +123 mV Electrical Force + + + - - - - + - - + Net Net 0 mV Force 0 mV Force Ca2+ Ca2+ Ca 2+ Ca2+ Ca2+ Ca2+ Ca2+ Ca2+ 2+ Ca2+ Ca2+ Ca 2+ Ca Ca 2+ Ca2+ V 3m Ca2+ Ca2+ Ca2+ Cl- Cl- Cl- Cl- Ca2+ Ca2+ 2+ Ca2+ Chemical Force (diffusional) Cl- Cl- ClClCl- mV 65 Ca -12 Ca2+ + - ClCl- Cl- Chemical Force (diffusional) 13 What would happen to the resting membrane potential if extracellular K+ suddenly increased? Why? • If extracellular K+ suddenly increased (known as hyperkalaemia), EK driving K outward would be reduced (ie become less negative). Because EK is the major determinant of the RMP, the RMP would become less negative. Click to see answer • Extra credit: However, this depolarisation paradoxically leads to Decreased excitability (not increased, as predicted) because the long term depolarisation inactivates Na+ channels, so it is harder to reach threshold 14 Give an example of a local anaesthetic and explain how they work. • Lidocaine (lignocaine). These block sodium channels, which raises the threshold of action Click to see answer potentials and thus lowers local excitability 15 Conduction Velocity 16 What is the clinical importance of measuring conduction velocity? • This is measured to investigate the source of motor weakness in arms and legs. • It can detect gross pathological changes such as conduction block and conduction slowing, which could Click to see answer signify demyelination or degeneration. It can help diagnose: Peripheral neuropathy, Carpal tunnel syndrome, Spinal disc herniation, etc. 17 What is the conduction velocity for an alpha motor neuron? • 100 meters/second Click to see answer 18 What is the conduction velocity for C fibres for pain? • 1 meter/second Click to see answer 19 What are the structural differences between alpha motor neurons and C fibres responsible for the difference in their conduction velocity? Explain which structural features increase and which decrease conduction velocity. • Alpha is large diameter and myelinated, both of which increase conduction velocity. C fibres are small and unmyelinated. • Myelination increases transmembrane resistance, which leads to more efficient electrotonic Clickaxon to see between answer signalling inside the nodes of Ranvier. • Increased diameter leads to increased conduction velocity because intracellular resistance along the length of the axon is lower. This leads to more efficient (hence faster) electrotonic transmission. 20 What are the Nodes of Ranvier and what is their purpose? • • The nodes of Ranvier are thin, unmyelinated strips of membrane along the length of a myelinated axon. The “bare” cell membrane at the node is specialised for detecting a distant transmembrane electric field (electrotonically) and then firing an action potential in response to it. – • • The membrane at a Node is excitable (because Na+ channels are clustered there), while membrane under myelin notsee excitable (they do not have clusters of Na Clickisto answer channels). Nodes of Ranvier are essential to increasing conduction velocity by having action potentials “jump” from one node to the next – socalled saltatory conduction. Electrotonic transmission is much faster than starting an action potential, but electrotonic transmission is limited by distance because the signal gets smaller as it travels further from its origin 21 Synaptic Transmission 22 How are electrical synapses molecularly coupled? • Via gap junctions • Remember: most synapses are chemical synapses (NOT electrical); chemical synapses transmit signals by releasing neurotransmitter from the pre-synaptic terminal, which is detected by receptors on the postsynaptic membrane Click to see answer 23 How do neurons encode intensity of a signal? • Increased frequency, or different neurons for different signal strengths Click to see answer 24 If a neuron was regularly being stimulated but to a subthreshold potential, would it be possible for a subthreshold stimulus onto that neuron via a different synapse to cause an action potential? Why? What is this issue called? • The phenomenon where two different inputs to a neuron, which are both subthreshold, lead to an action potential is called spatial summation. What happens is that each stimulus partially depolarizes the membrane Click to see answer when creating the EPSP. Each increase in voltage takes that part of the membrane closer to threshold. 25 Give an example of a selective serotonin reuptake inhibitor and explain how they work. • SSRIs are antidepressants. They include fluoxetine (Prozac), paroxetine, citalopram and fluvoxamine. • SSRIs block the normal reuptake of serotonin from the synapticClick cleft. to see answer • Thus, whenever serotonin is released into the synapse, serotonin builds up in the synaptic cleft, leading to an increase in signalling at serotonin based synapses 26 Screencasts Explaining Equilibrium Potential • Part 1 – http://youtu.be/f3JEyg7WgOo • Part 2 – http://youtu.be/wXO-CCEm5eU • Part 3 – http://youtu.be/6cZFSEmp9lQ • Part 4 – http://youtu.be/haHR-Y_0xiA • Graded Potentials & Electrotonic Conduction These show how total force on an ion is the Sum of the Chemical And Electrical Forces on that ion, and they demonstrate how best to draw this on an exam. – http://youtu.be/N4Z_Bl337BQ 27 Screencast explaining to draw an Action Potential on an Exam – http://youtu.be/ETm_ZCHJ0Nc 28 Extra Slide: Electrotonic Conduction Passive conduction of voltage Brief channel opening allows ions to flow is depolarised here Decreased by Resistance Myelin: High resistance Shields electric field  + +   + + Now membrane    + + Cytoplasm: Low resistance Instantly transmits electric field Basis of: saltatory conduction, all summation, graded potentials Larger diameter  Lower resistance  faster conduction 29