Action Potential PDF

Action Potential RESTING MEMBRANE POTENTIAL A membrane potential results from separation of positive and negative charges across the cell membrane The difference in potential across the cell membrane can be measured by special devices (e.g. the Cathode Ray Oscilloscope). In neurons, the rest...

Action Potential RESTING MEMBRANE POTENTIAL A membrane potential results from separation of positive and negative charges across the cell membrane The difference in potential across the cell membrane can be measured by special devices (e.g. the Cathode Ray Oscilloscope). In neurons, the resting membrane potential is usually about –70 mV. Causes of the RMP: a- Potassium efflux b- The Sodium- potassium pump c- ICF non diffusible anions The Goldman-Hodgkin-Katz Equation (Goldman equation) can be used for direct calculation of the RMP. It includes the effects of the major ions and their permeabilities (P) across the cell membrane; as follows: RMP (mv) =  61 log PK [K]ECF + P Na [Na]ECF + PCl [Cl]ICF  PK [K]ICF + P Na [Na]ICF + PCl [Cl]ECF The magnitude of the RMP differs in different types of cells, for example: In a skeletal and cardiac muscle cell = - 90 mv In a nerve cell = - 70 mv Action potential It is characteristic of Excitable tissues (muscles and nerves) Definition of Action potential; It is a rapid, short lived, change in the membrane potential in the form of depolarization followed by repolarization, that spread along the membrane. The components of the action potential  Polarization(Resting state):during rest the inside of the cell membrane is more negative than the outside  De polarization:  The inside of the membrane becomes more positive compared to the outside of the membrane  Re polarization:  The inside of the membrane becomes more negative than the outside  Approaching the RMP The membrane Spike potential +35 mV potential in mV Zero potential line The threshold The firing level The RMP = -70 mV After hyper polarization Stimulus Time ms Ionic basis of the Action potential Excitable cells have voltage-gated Na+ channels and voltage-gated K+ channels which can explain the events in the action potential The firing level (threshold potential) is the depolarization level which can stimulates the opening of both voltage-gated Na+ and voltage- gated K+ channels Voltage gated Na+ channels are fast channels, they open very fast and are rapidly closed Voltage gated K+ channels are slower, their opening is slow and their closing is delayed Ionic basis of Depolarization phase During the resting state, before the action potential begins, the conductance for potassium ions is 50 to 100 times as great as the conductance for sodium ions. Depolarization is due to opening of voltage gated Na+ channels when sodium channels become activated and allow up to a 5000-fold increase in sodium conductance. Na+ diffuses into the cell (Na+ influx) and the inside of the cell membrane becomes less negative and even positive compared to the outside. Voltage gated Na+ channels close rapidly and the influx of Na+ stops. Ionic basis of the repolarization phase Opening of Voltage gated Ka+ channels is slower than the opening of Na+ channels K+ channels are open at the tip of the spike potential Opening of K+ channels allows the outward diffusion of K+ ions (K+ efflux) down its concentration gradient K+ efflux results in rapid repolarization Ionic basis of the after hyperpolarization The slow closing of K+ channels explain the period of hyper-polarization: Continuous out ward K+ efflux makes the cell membrane hyperpolarized Finally, when the channels are closed, and K+ permeability is back to its normal resting state, the membrane gradually returns to its RMP.  Closure of Na+ The membrane channels potential in Opening of k+ channels +35 mV mV Depolarization Zero Repolarization Influx of Efflux of Na+ K+ Opening of The threshold voltage potential = -55 mV gated Na+ The RMP = -70 mV channels After Hyper polarization Stimulus Time in mSeconds The role of Na+/K+ AtPase pump in action potential Na+, K+ ATPase pump have NO role in depolarization or repolarization phase of the action potential or in the return to the RMP But, during the action potential: 1. Na+ ions inter the cell in depolarization (inc. ICF Na+) 2. K+ ions leave the cell in repolarization ( dec. ICF K+)  So that after prolonged repeated stimulation the ICF concentration of these two ions become different  The Function of the Na+, K+ ATPase pump is to restore the normal ICF concentration of Na+ and K+ after prolonged repeated stimulations. (recharge the nerve) Characters of the action potential 1. The action potential shows the ( All or None ) character 2. The action potential have a refractory period 3. The action potential is a propagated (conducted) response.  1- The All or None character of the Action Potential  Only the stimuli which can reach the threshold or above can elicit an action potential which is always the same and is propagated 1. Sub- threshold stimulation will not cause an action potential 2. If the threshold potential was reached a full propagated action potential will occur 3. The elicited action potential is always the same regardless off the strength of the supra-threshold stimulus (their is no bigger or smaller action potentials) The membrane potential in +35 mV mV Zero Action Opening of all potential Na+ channels Local potential -55 mV -70 mV XX XXXX XXXXXX Sub-threshold Stimulus Threshold Stimulus Time 2- The refractory period During an ongoing action potential the neuronal cell can not be stimulated to generate another action potential Absolute refractory period: The period during which no stimulus no mater how strong it was, can stimulate an action potential = Most of the duration of the spike potential Relative refractory period: A very strong stimulus can cause an action potential = the last part of the spike potential (when repolarization is almost complete) The membrane potential in +35 mV mV Zero Action potential -55 mV -70 mV XX XXXX XX XXXX Time The Different states of voltage-gated Na+ channels V-G Na+ channels go through three different states during the action potential; 1. Closed Resting state 2. Open ( activated) state 3. Closed Inactivated state The reason of these three states is that the Na+ channels have two gates:  One is located in the outside of the cell = Activation gate  Another gate is located in the inside of the cell = Inactivation gate  During Depolarization phase Activation gate Inactivation gate Depolarization 1st : The Na+ channel is Activated = Open 2nd : The Na+ channel is inactivated = Closed 1st = Resting State = 2nd =Activated State Resting membrane p. = Depolarization 3rd = Inactivated State = Repolarization 1. At the threshold both gates are opened and the Na+ channels are in the activated , open state, influx of Na+ causes rapid depolarization  During most of repolarization the Na+ channels are in the inactivated state 1. The outer activation gate is open 2. The inner inactivation gate is closed  Closed Na+ channels in the inactivated state can not be stimulated to open (refractory period)  Na+ channels are back to the resting state when the membrane potential is repolarized back to or very near to the RMP  Na+ channels in this state can be stimulated 3- The action potential can be propagated How is the action potential propagated along the membrane? An action potential occurring at any point of an excitable membrane can excite adjacent areas of the membrane How is the action potential propagated along the membrane ? 1. At the site of stimulation the action potential will create a local positive area inside the cell membrane and a negative area in the outside 2. The un-stimulated neighbouring areas have negative charges inside the cell membrane and positive charges in the outside. 3. Positive charges inside and outside the membrane will diffuse toward the negative areas causing circular local currents 4. The local currents causes a depolarizing local response that when it reaches the threshold, a new action potential is generated and propagated in the same manner  Initial Action New Action potential New Action potential potential +v +v +v +v -ve +v +v -ve +v +v +v +v e e e e e e e e e e -ve -ve -ve -ve +v -ve -ve -ve -ve -ve -ve e -ve +v = polarization = generates Action e potential Saltatory  Conduction Some nerve fibers are surrounded by Myelin Sheath (Myelinated nerve fibers)  Myelin is a lipid structure that acts as an electrical insulator  In Myelinated nerve fibers the myelin sheath is not continuous. Instead there are gabs in the myelin sheath occurring in constant distances from each other called the nodes of Ranvier  Voltage gated Na+ channels are highly concentrated in the nodes of Ranvier Rate of conduction of The AP in nerve fibers Conduction of action potential in myelinated nerve fibers is 50 times faster than in unmyelinated nerve fibers The action potential can be conducted in a speed varying from 90m/ to 0.5 m/s The degree of myelination is most important factors that determines the speed of conduction Changes in the excitability of the neuronal and muscle cells under the Effect of changes in ECF ions concentrations Changes in the threshold potential: 1. The threshold potential depends on the state of Na+ channels 2. Na+ channels are stabilized by Ca2+ Decreased ECF Ca2+ (hypo-calcemia) increases the excitability of nerves and muscles. Increased ECF Ca2+ (hyper-calcemia) decreases the excitability of nerves and muscles. The membrane potential in mV +35 mV Zero Opening of Na+ channels The threshold potential = -55 mV The threshold in X hypocalcemia X X X The RMP = -70 mV Stimulus Time in ms Changes in RMP: 1. Normal RMP is mainly determined by K+ permeability 2. RMP is affected by ECF K+ concentration 3. If decreased ECF K+ the RMP was more negative than normal (decreased RMP= hyperpolarized) the neuron will be less excitable (Hypokalemia) 4. If increased ECF K+ the RMP was less negative than normal (increased RMP) the neuron will be more excitable 5. Hyperkalemia is a very dangerous conditionThe most serious and fatal complication of hyperkalemia is on the excitability of cardiac muscles Disturbances in sodium ions  Have little effect on the resting membrane potential (RMP).  Hyponatremia decreases the amplitude of the action potential.