Topic 4 - Resting and changing membrane potential e7f9d749485546f39db7be5fc903e576.pdf

🛌🏾 Topic 4 - Resting and changing membrane potential + Action Potential What is the Value of Resting Membrane Potential All or nothing = amplitude/strength is the same, pattern & frequency changes...

🛌🏾 Topic 4 - Resting and changing membrane potential + Action Potential What is the Value of Resting Membrane Potential All or nothing = amplitude/strength is the same, pattern & frequency changes only Resting membrane potential (RMP) (-65mV) Voltage across the membrane at rest within the cell (inside) What 3 factors are responsible for unequal distribution of inorganic ions between intracellular & extracellular fluid permeability concentration gradient electrical gradient of Na+, K+, Cl- + organic ions Function of Non-Gated (leak) Ion Channels sets Resting Membrane Potential channels are always open (more K+ channels than Na+ channels) Topic 4 - Resting and changing membrane potential + Action Potential 1  highly permeable to K+ Function of Voltage-Gated Ion Channels change in voltage causes ion channels to open, huge influx of ions generates action potentials Function of Ligand-Gated (chemical) Ion Channels generate potential changes at synapses Explain how the electrical gradient works and is self limiting Initial Conditions: Higher concentration of K+ inside the cell compared to outside. Other ions and anions present, but unable to cross the membrane. Movement of K+: When K+ channels open, K+ moves down its concentration gradient and exits the cell. Each exit of K+ reduces positive charge inside, creating a slight excess of positive charge outside. Charge Imbalance: Excess positive charge outside causes a slight excess of negative charge inside. Inside of the cell becomes negative relative to the outside. Electrical Potential Difference: Establishment of an electrical potential difference across the membrane. Like charges repel, making it harder for remaining K+ ions to leave, opposing their movement down the concentration gradient. (electrostatic repulsion) Electrochemical Gradient: Electrical and diffusional forces jointly form the electrochemical gradient for K+. Electrochemical gradient determines the spontaneous direction of K+ movement. Equilibrium: Topic 4 - Resting and changing membrane potential + Action Potential 2  As the electrical potential difference builds up, it opposes further K+ movement out of the cell. Eventually, the electrical force driving K+ back into the cell equals the chemical force driving K+ out. System reaches equilibrium - no net movement of K+ in either direction. Continuous Balance: Every time one K+ leaves, another enters, maintaining the equilibrium. - At Ek : net concentration = net electrical ,no flow - Equilibrium potential for potassium (Ek) : In this case RMP = Ek = -75mv. (it is normally more negative inside) What is the Nernst Equation The equilibrium potential for a single ion can be calculated using the Nernst equation R and F are constants , T = Body Temp. (kelvin), z = Valency , [ion]o = outside ion conc, [ion]i = inside ion conc. If membrane is only permeable to K+ : Em (membrane potential) = Ek (will be negative) At this voltage, forces equal - no net movement of K+ Topic 4 - Resting and changing membrane potential + Action Potential 3  What is Hyperkalaemia and why is it dangerous to a person higher than normal potassium levels in the blood heart may stop beating cardiac arrythmias altered excitability Significance of Potassium Membrane potential particular sensitive to changes in potassium. Increasing external potassium depolarises the membrane. Neuronal K+ is under tight regulation. What is the concentration of K+ in the blood 4mM Lecture 2 - Action Potential Explain a general overview of Action Potential 1. Initial stimulus – initial depolarisation that triggers due to the movement of Na+ into the neurone by ligand gates cation channels 2. Depolarisation – If initial depolarisation reaches the threshold level, (-55 mV). voltage-gated Na+ channels (VGSCs) open which results in rapid depolarisation (Na+ influx) Topic 4 - Resting and changing membrane potential + Action Potential 4  3. Repolarisation – VGSCs become inactivated and voltage-gated K+ channels open. the membrane becomes more negative due to K+ efflux 4. Hyperpolarisation – cell ‘overshoots’ the repolarisation phase due to the movement of K+, resulting in hyperpolarisation, before returning back to the resting membrane potential. (Some VG K+ channels still open, All K+ leak channels open) 5. back to rest (-70mv) all VG K+ CP close. What are the 3 states of VGSC (Voltage-Gated Na+ Channels) Closed State = -70 mV (resting) Open State = -50 to +30 mV (depolarisation) Inactivated State = +30 to -70 mV (repolarisation) How does VGSC go from Inactivated to Open State VGSCs (Voltage-Gated Sodium Channels) inactivate after depolarisation is over. Topic 4 - Resting and changing membrane potential + Action Potential 5  In the inactivated state, Na+ ions cannot pass through the channel, into the neurone To become open again, the channel must recover into the closed state. This process creates the refractory period. Define “refractory period” and state the 2 types of refractory periods describes the period of time in which the cell cannot generate an action potential Absolute + Relative Refractory Periods What are the effects when Local What is the Absolute Refractory Anaesthetics are applied to nerves Period (hint: Action Potential) The period of time measured Local anaesthetics are drugs (weak from the onset of the action bases) that reversibly block sodium potential, during which another channel in their inactivated state — action potential cannot be > block nerve conduction —> triggered Prevents Pain Explanation: Na+ channels Delay to threshold inactivated, K+ channels open slow rate of rise of action potentials reduce rate of action potential conduction eventual failure of action potentials Routes: Surface application, Cream, Epidural, Intradermal Injection Topic 4 - Resting and changing membrane potential + Action Potential 6  What is the Relative Refractory Period AP if stronger stimulus The period of time following an action potential during which more depolarising current is required to achieve the threshold than normal This is because the VGSCs are beginning to recover,, some are still inactive. The relative refractory period ends when all Na+ channels have recovered. Some Na+ channels still inactivated More K+ channels open → needs more stimulus to overcome large gK (conductance of K+) Explain how propagation of action potential occurs? Action potential propagation is essential for transmitting signals along the entire length of the axon. Local spread of current triggers the generation of new action potentials along the axon. According to local current theory: Depolarization at a specific point in the membrane initiates a spread of depolarization in the surrounding membrane area. Influx of Na+ ions repels other positive ions, leading to local depolarization. The strength of the current weakens as it spreads further along the membrane. Topic 4 - Resting and changing membrane potential + Action Potential 7  What 2 factors does Conduction Velocity Depend on? 1) Diameter of axons larger diameter = faster conduction 2) Myelination: unmyelinated - 0.1 metres / sec myelinated - 100 metres / sec → faster conduction Explain how Saltatory Conduction works Small, unmyelinated portions of the axon are referred to as Nodes of Ranvier, Ion channels are exclusively present here Action Potential jumps from node to node → allows faster propagation Electron micrograph of a transverse section of the myelin sheath Topic 4 - Resting and changing membrane potential + Action Potential 8  After using the Nernst Equation, the K+ Equilibrium potential is -94.6mV, but the actual membrane potential of the same nerve cell is -75mV. Why are these values different? Permeability to other ions is present (Na+, Cl-) Nernst Equation only considers K+ ions only Some neurotransmitters act to increase Cl- conductance in the postsynaptic cell. What are the consequences of an increased Cl- conductance for the membrane potential? Hyperpolarisation - increased negative charge Inhibitor of excitability → makes it harder to generate an action potential The membrane potential is restored rapidly to resting levels in nerve and muscle cells after an action potential. How is this achieved? Increased Potassium conductance by opening of VG K+ Channels Topic 4 - Resting and changing membrane potential + Action Potential 9