Membrane and Action Potential 2021 PDF

MEMBRANE POTENTIAL & ACTION POTENTIAL NG SOOK LUAN (Ph.D, UKM) [email protected] 012-9305208  LEARNING OBJECTIVES 1. Explain the genesis of resting membrane potential. 2. Explain equilibrium potentials of important ions. 2 The membr...

MEMBRANE POTENTIAL & ACTION POTENTIAL NG SOOK LUAN (Ph.D, UKM) [email protected] 012-9305208  LEARNING OBJECTIVES 1. Explain the genesis of resting membrane potential. 2. Explain equilibrium potentials of important ions. 2 The membrane potential results from a separation of positive & negative charges across the cell membrane  Equilibrium Potential Describes voltage across cell membrane if only 1 ion could diffuse If membrane permeable only to K+, it would diffuse until it reaches its equilibrium potential (Ek) K+ is attracted inside by trapped anions but also driven out by its concentration gradient At K+ equilibrium, electrical and diffusion forces are = and opposite Inside of cell has a negative charge of about -90mV  Nernst Equation (Ex) Gives membrane voltage needed to counteract concentration forces acting on an ion Value of Ex depends on ratio of ion concentrations inside and outside cell membrane Ex = 61 log [Xout] ; z = valence of ion X z [Xin] For concentrations shown at right: EK+ = 61 log 5 +1 150 = -90mV ENa+ = 61 log 145 +1 12 = +60mV  Resting Membrane Potential ( RMP ) Excess of positive charges outside and ICF ECF negative charges inside the membrane The value RMP is about: -70 mV for Neuron -80 mV for Cardiac muscle -90 mV for Skeletal muscle  Resting Membrane Potential (RMP) At rest, all cells have a negative internal charge = RMP Membrane voltage of cell not producing impulses RMP of most cells is –65 to –85 mV Results from: Unequal distribution of ions Large cations being trapped inside cell [K+ is major ICF cation & Na+ is major ECF cation] Na+/K+ pump and limited permeability keep Na+ high outside cell K+ is very permeable and is high inside cell; attracted by negative charges inside The cytoplasm contains anions (Proteins, A-) which cannot diffuse through the membrane.  Resting Membrane Potential (RMP) continued Some Na+ diffuses in so RMP is less negative than EK+  Role of Na+/K+ Pumps in RMP Na-K pump: an active pump Because 3 Na+ are pumped out for every 2 K+ taken in, pump is electrogenic It adds about –3mV to RMP Summary of Processes that Affect the Resting Membrane Potential Figure 10.12  LEARNING OBJECTIVES 3. Define local response and firing threshold. 4. Explain the formation of action potential, its characteristics and factors affecting it. 5. Explain conduction of impulses along an axon. 6. Define compound action potential.  Excitability Excitable cells can discharge their membrane potential quickly By rapid changes in permeability to ions Neurons and muscles do this to generate and conduct impulses Membrane Potential Changes Measured by placing 1 electrode inside cell and 1 outside Depolarisation occurs when MP becomes more positive than RMP Hyperpolarisation: MP becomes more negative than RMP Repolarisation: MP returns to RMP  Selective Permeability of Membranes Non-gated ion channels / Leak channels Some ions are permitted to cross more easily than others. Ion channels stay open all the time (non-gated). Gated ion channels Gates can be opened or closed in response to a triggering event – change in the protein conformation of the channel. * Triggering event – changes in membrane permeability, altering ion flow across membrane 1. Voltage-gated - changes in membrane potential 2. Ligand/Chemically gated – binding of a specific extracellular chemical messenger to a surface membrane receptor 3. Mechanically gated – stretching or other mechanical deformation 4. Thermally gated – local changes in temperature (hot or cold)  Membrane Ion Channels MP changes occur by ion flow through membrane channels Some channels are normally open; some closed K+ leak channels are always open Closed channels have molecular gates that can be opened Voltage-gated (VG) channels are opened by depolarization VG K+ channels are closed in resting cells VG Na+ channels are closed in resting cells A triggering event at some point along the membrane opens some of the sodium channels, allowing some sodium ions to enter the ICF from the ECF. This initiates a graded depolarization of the cell locally where the triggering event occurs. The stronger the triggering event, the more sodium channels open and the greater the local depolarization as more sodium enters the cell.  Local Potential Changes Polarized: has potential due to the charges are separated across the plasma membrane Depolarized: the membrane potential becomes less negative/ less polarized; the inside is less negative than RMP Local potentials: Graded potential. Short distance signals. The amount of change in potential is proportional to the intensity of the stimulation. Hyperpolarized: membrane potential becomes more negative than RMP. Threshold potential: level of stimulation to generate an action potential. LOCAL POTENTIAL / GRADED POTENTIAL Ligand gated channels – open with chemical stimulation (dendrites or body of the cell) Once Ach binds to the ligand gated Na+ channels, channels open, high conc. of Na+ (extracellular) inflow to the cell, K+ outflow from the cell – local depolarisation / local potential. Local depolarisation decays with distance from stimulus (from dendrites/body to hillock) If the stimulus is strong enough or the amount of Ach is enough, the depolarisation reaches hillock, generate local current to invert the polarisation of the entire body of neuron - depolarisation reaches threshold (-55mV)  Action Potential The action potential causes an electrical current that stimulates adjacent regions. Series of action potentials occur sequentially along the length of the nerve (impulse propagation).  Mechanism of Action Potential Depolarisation: At threshold, VG Na+ channels open (fast to open) Na+ driven inward by its electrochemical gradient This adds to depolarisation, opens more channels Termed a positive feedback loop Causes a rapid change in MP from –70 to +30 mV Repolarization: VG Na+ channels close; VG K+ channels open Electrochemical gradient drives K+ outward Repolarizes axon back to RMP * VG K+ channels slow to open and slow to close – causes the repolarization over shoot the RMP – HYPERPOLARIZATION  The Action Potential (AP) AP is a wave of MP change that sweeps along the axon from axon hillock to synapse Wave is formed by rapid depolarization of the membrane by Na+ influx; followed by rapid repolarization by K+ efflux Refractory Period - Refractory period:- short time following a nerve impulse that a threshold stimulus will not trigger another impulse. - There are two types of refractory period: Absolute Refractory Period - Na+ channels are inactivated and no matter what stimulus is applied they will not re-open to allow Na+ in & could not depolarise the membrane to the threshold of an action potential. Relative Refractory Period - Some of the Na+ channels have re-opened but the threshold is higher than normal making it more difficult for the activated Na+ channels to raise the membrane potential to the threshold of excitation. 26  Refractory Periods Absolute refractory period: Relative refractory period Membrane cannot produce occurs when VG K+ channels another AP because Na+ are open, making it harder to channels are inactivated depolarize to threshold  Characteristics of AP Once it is formed – will be propagated The size, amplitude, and velocity (speed) of an action potential are independent of the intensity of the stimulus that initiated it as long as above threshold. size or speed of action potential does not change if the stimulus intensity is above a threshold (supramaximum) More intense stimulus causes more FREQUENT firing without changing the magnitude. It obeys “All or None” Law Can’t be summated.  Action potentials are All-or-None When MP reaches threshold an AP is irreversibly fired Because positive feedback opens more and more Na+ channels Shortly after opening, Na+ channels close and become inactivated until repolarization  How Stimulus Intensity is Coded Increased stimulus intensity causes more APs to be fired Size of APs remains constant  Propagation of the Action Potential Action Potential spreads down the axon in a chain reaction Unidirectional in vivo Refraction prevents spread back across axon Speed of propagation varies with the axon diameter ie. Faster with larger and thick axons In large axons of mammals 5m/second 2um axons 20m/second in 20um axons Speed of propagation also assisted by the myelin sheath Ie. Faster in myelinated axons… known as ‘saltatory conduction’ ie. Impulse jumps from one “Nodes of Ranvier” to another It increases conduction speed up to 15 times  Axon Conduction Axon’s properties affect its ability to conduct current Includes high resistance of cytoplasm Resistance decreases as axon diameter increases  Conduction in an Unmyelinated Axon After axon hillock reaches threshold and fires AP, its Na+ influx depolarizes adjacent regions to threshold Generating a new AP Process repeats all along axon So AP amplitude is always same Conduction is slow  Conduction in Myelinated Axon Ions can't flow across myelinated membrane Thus no APs occur under myelin and no current leaks This increases current spread  Conduction in Myelinated Axon Gaps in myelin are called Nodes of Ranvier APs occur only at nodes VG Na+ channels are present only at nodes Current from AP at 1 node can depolarize next node to threshold Fast because APs skip from node to node Called saltatory conduction