Membrane potential and Action potential 2023.pptx

Membrane Potentials and Action Potentials  Generation of Resting Membrane Potential (-70mV) Introduction: Nerves and muscles are called excitable tissue because they respond to: a) Chemical. b) Mechanical. c) Electrical stimuli. Muscles demonstrate by contraction, while n...

Membrane Potentials and Action Potentials  Generation of Resting Membrane Potential (-70mV) Introduction: Nerves and muscles are called excitable tissue because they respond to: a) Chemical. b) Mechanical. c) Electrical stimuli. Muscles demonstrate by contraction, while nerves by integration and transmission. Electrical signals in neurons: Production of signals depend on two basic features of the plasma membrane of excitable cells: i) Resting membrane potential. ii) Ion channels.  I) Ion channels: Ion channels open and close due to the presence of (gates). There are four kinds of ion channels: 1 leakage channels: open and close randomly 2 Voltage-gated channels: opens to a change in Membrane Potential (voltage). 3 Ligand-gated channels: opens and close in response to chemical stimulus, such as Ach. 4 mechanical gated channels: open or  II) Resting membrane potential(RMP): Definition: The difference in voltage across the cell membrane when a neuron or muscle cells is not producing an Action Potential. A typical value is: -70 mV(-50 to - 90) A cell that exhibits a membrane potential is said to be polarized. Why RMP is negative inside the cell relative to the outside? Because of the following:- 1- the resting membrane is 10-100 times more permeable to K+ than to Na+. Potassium inside the cell is 140meq/L and outside is 4meq/L. K+ tends to leak out of the cell down its concentration gradient, carrying +ve charge with it, and unable to carry Cl- with it because Cl- has higher concentration outside. Forces act on cell membrane at rest: 1 Diffusion: is the movement of molecules from a region of higher concentration to a region of lower concentration. 2 Electrical gradient: +ve ions move to the –ve area and –ve ions move to +ve area 3 Active transport: transport ions against their concentration gradient. Most important example is Na+_K+ pump(need energy); responsible for the transport of 3 Na+ to the outside and 2 K+ to the inside. i- The maintenance of the RMP ii- The development of the The action potential (AP): Definition: The Action Potential is a sudden reversal of membrane polarity by a stimulus. Importance: AP occurs in living organism to produce physiological effects such as: 1. Transmission of impulses along nerve fibers 2. Release of neurosecretions or chemical transmitters in synapses. Action  potential takes place as a result of the triggered opening and subsequent closing of 2 specific types of channels Voltage  gated Na+ channels REMEMBER: IMPORTANT: Sodium voltage-gated channels: are fast channels & have 2 gates: - An outer Activation gate(closed in resting state) - An Inner Inactivation gate(open in resting state) Potassium channels are slow channels & have only ONE gate. These channels are different from Sodium & Potassium leak channels. The Sodium-Potassium PUMP is present separately.  Voltage gated Na+ channels  Most important channels during AP I t has two gates: ACTIVATION  GATES: At RMP activation gates are closed so no Na+ influx at RMP through these channels These  activation gates open when membrane potential become less negative than during resting state, then the activation gates of these voltage gated channels open so  Activation of the Sodium Channel When the membrane potential becomes less negative the resting state, rising from −90 millivolts toward zero, it finally reaches a voltage—usually somewhere between −70 and −50 millivolts— that causes a sudden conformational change in the activation gate, flipping it all the way to the open position. During this activated state, sodium  Inactivation of Na+ channels T h e s a m e increase in voltage also closes the inactivation gates but closing of gates is a slower process than opening so large amount of Na+ influx has occurred. Therefore, after the sodium channel has remained open for a few 10,000ths of a second, the inactivation gate closes and sodium ions no longer can pour to the inside of the membrane. At this point, the membrane potential begins to return toward the resting membrane state, which is the repolarization process. Another  important feature of Na+ channels inactivation is that the inactivation gate will not reopen until the membrane potential returns to or near the original RMP.  Voltage gated K+ channel During  RMP Voltage gated K+ channels are closed T h esame stimulus which open voltage gated Na+ channels also open voltage gated K+ channel D u eto slow opening of these channels they open just at the same time that the Na+ channels are beginning to close because of inactivation. S onow decrease Na+ influx and simultaneous increase in K+ out flux cause  Phases of action potential Depolarization Repolarization Hyperpolarizatio n  Initiation of action T o potential initiate an AP a triggering event causes the membrane to depolarize from the resting potential of -90 mvs. Depolarization  proceeds slowly at first until it reaches a critical level known as threshold potential. i.e. -65 mvs. At threshold explosive depolarization occurs. An AP will not occur until the initial rise in membrane potential reaches a threshold  IONIC BASIS OF AN ACTION POTENTIAL: 1. DEPOLARIZATION: Sodium (Na) Influx 2. REPOLARIZATION: Potassium (K) Efflux 3. HYPERPOLARIZATION: Leakage of excess Potassium (K) ions through the slow closing K channels. 4. RETURN OF THE AP TO THE RMP FROM HYPERPOLARIZATION: Sodium-Potassium Pump  State of SODIUM channel gates: Resting state: - Inactivation gates: OPEN - Activation gates: CLOSED Depolarization: - Activation gates: OPEN - Inactivation gates: OPEN Peak: - Inactivation gates: CLOSED - Activation gates: OPEN Repolarization: - Inactivation gates: OPEN - Activation gates: CLOSED  DEFINITION: LATENT PERIOD: It is the time period between the application of a stimulus and the start of the response (Action Potential). Propagation of Action Potential  single action potential involves only a small portion of the total excitable cell membrane and then action potential the is self- propagating moves away from and the stimulus (point of origin)  Direction of Action potential A P travels in all directions away from the stimulus until the entire membrane is depolarized  Conduction of Action T w o Potentials types of propagation Contiguous  conduction  Conduction in unmyelinated fibers  Action potential spreads along every portion of the membrane Saltatory  conduction  Rapid conduction in myelinated fibers  Impulse jumps over sections of the fiber covered with insulating myelin  Unmyelinated Nerve fiber Once an action potential is initiated at the axon hillock, no further triggering event is necessary to activate the remainder of the nerve fiber. The impulse is automatically conducted throughout the neuron. For the action potential to spread from the active to the inactive areas, the inactive areas must somehow be depolarized to threshold. This depolarization is accomplished by local current flow between the area already undergoing an action potential and the adjacent inactive area This depolarizing effect quickly brings the involved inactive area to threshold, at which time the voltage-gated Na channels in this region of the membrane are all thrown open, leading to an action potential in this previously inactive area. Meanwhile, the original active area returns to resting potential as a result of K efflux.  VIVA Question: Does the action potential become weak (decremental) as it travels down the nerve fiber? NO, the action potential does NOT become weak as it travels down the nerve fiber. In fact, the AP does NOT travel down the nerve fiber but triggers a new AP in every new part of the membrane. It is like a “wave” at a stadium. Each section of spectators stands up (the rising phase of an action potential), then sits down (the falling phase) in sequence one after another as the wave moves around the stadium. The wave, not individual spectators, travels around the stadium. Thus, the last action potential at the end of the axon is identical to the original one, no matter how long the axon is. In this way, action potentials can serve as long-distance signals without becoming weak or distorted or decremental.  VIVA Question: Why does NOT the action potential spread in the reverse direction? If AP were to spread in both directions, which is forward and backward, it would be chaos, with the numerous AP’s bouncing back & forth along the axon until the axon eventually fatigued. This does not happen due to the Refractory period. During and after the generation of an AP, the changing status of the voltage-gated Na and K channels prevents the AP from being generated in these areas again. CONDUCTION OF AP IN A MYELINATED NERVE FIBER:  Continuous Conduction Occurs in unmyelinated axons. In this situation, the wave of de- and repolarization simply travels from one patch of membrane to the next adjacent patch. In a Myelinated Nerve Fibre an Action Potential travels by SALTATORY Conduction, which is in a jumping manner from one Node of Ranvier to the next Node of Ranvier, While in an Unmyelinated Nerve Fibre an Action Potential travels from POINT TO POINT. At the nodes of ranvier, there are an increased number of Sodium  Which do you think has a faster rate of AP conduction – myelinated or unmyelinated axons?  The answer is a myelinated axon. If you can’t see why, then answer this question: Could you move 100ft faster if you walked heel to toe or if you bounded in a way that there were 3ft in between your feet with each step?  Which do you think would conduct an AP faster – an axon with a large diameter or an axon with a small diameter?  The answer is an axon with a large diameter. If you can’t see why, then answer this question: Could you move faster if you walked through a hallway that was 6ft wide or if you walked through a hallway that was 1ft wide? Name the events & ions responsible for: – Depolarization – Repolarization – Hyperpolarization – Return of the AP to the RMP  Principles of Action 1. Potentials The All or Nothing Principle: Once an action potential has been elicited at any point on the membrane of a normal fiber, the depolarization process travels over the entire membrane if conditions are right, but it does not travel at all if conditions are not right. This principle is called the all-or-nothing principle, and it applies to all normal excitable tissues. 2. The Refractory Period: Responsible for setting up limit on the frequency of Action Potentials  1. ALL OR NONE LAW (also called the All or Nothing Law) On application of a stimulus, an excitable membrane either responds with a maximal or full-fledged action potential that spreads along the nerve fiber, or it does not respond with an action potential at all. This property is called the all-or-none law. (This is in direction proportion to the strength of the stimulus applied.) e.g: This is similar to firing a gun. Either the trigger is NOT pulled sufficiently to fire the gun (subthreshold stimulus) OR it is pulled hard enough to fire the gun (threshold is reached). Squeezing the trigger harder does not produce a greater explosion, just as pulling the trigger halfway does not cause the gun to fire halfway.  All-or-None Principle If any portion of the membrane is to threshold an AP is initiated which will depolarized go to its maximum height. A triggering event stronger than one necessary to bring the membrane to threshold does not produce a large AP. However a triggering event that fails to depolarize themembrane to threshold does not trigger the AP at all.  All or none principle Thus  an excitable membrane either respond to a triggering event with maximal Action potential that spread throughout the membrane in a non decremental manner or it does not respond with an AP at all. This is called all or none law. Importan ce T h eimportance of threshold phenomenon is that it allows some discrimination b/w important and unimportant stimuli. Stimulustoo weak to bring the membrane potential to threshold do not initiate action potentials and therefore do not transmit the signals.  Some Action Potential Questions What does it mean when we say an AP is “all or none?” – Can you ever have ½ an AP? How does the concept of threshold relate to the “all or none” notion? Will one AP ever be bigger than another? – Why or why not? 2. Refractory period: - ABSOLUTE REFRACTORY PERIOD - RELATIVE REFRACTORY PERIOD  2a: ABSOLUTE REFRACTORY PERIOD Definition: Once an action potential has been generated , the time period during which even a suprathreshold stimulus will fail to produce a new action potential is called the Absolute Refractory period. During this time the membrane becomes completely refractory (‘stubborn’ or ‘unresponsive’) to any further stimulation. It corresponds to the entire Depolarization phase & most of the Repolarization phase. Due to Absolute refractory period, one AP must be over before another can be initiated at the same site. APs cannot be overlapped or added one on top of  BASIS OF AN ABSOLUTE REFRACTORY PERIOD: During the depolarization phase of AP, the voltage- gated Sodium channels have still NOT reset to their original position. For the Sodium channels to respond to a stimulus, 2 events are important: 1. Sodium channels be reset to their closed but capable of opening position. i.e: inactivation gates open and activation gates closed. 2. The Resting membrane potential must be re- established. 2b: Relative Refractory Period Definition: Following the absolute refractory period is seen a period of short duration during which a second action potential can be produced, only if the triggering event is a suprathreshold stimulus. This period is called the Relative Refractory Period. It corresponds to the last half of the Repolarization phase.  Basis of a Relative Refractory Period: An action potential can be produced by a suprathreshold stimulus because of the following reasons: 1. By the end of the repolarization phase, some Na channels have reset while some K channels are also still open. 2. Thus, a greater than normal triggering event (suprathreshold stimulus) is required to produce an AP.  What is the significance of the REFRACTORY PERIOD (both absolute & relative): 1. There is no fusion or summation of the action potentials. This intermittent, ie. Not continuous conduction of nerve impulses is one of the reasons why a nerve fibre can respond to continuous stimulation for hours without getting tired. Thus, it decreases fatigue in a nerve fibre. 2. The Action Potentials are produced separate from each other. So, a new AP is produced in each part of the nerve fibre. This ensures that the AP does not die out as it is conducted along the membrane. 3. Only a certain number of Action Potentials can be produced in a nerve fibre because the interval between any 2 action potentials cannot be shorter than the Absolute Refractory Period. This prevents fatigue of the nerve fibers and sets an upper limit on the maximum numbers of AP that can be produced in a nerve fibre in a given period of time. 4. By the time the original site has recovered from its refractory period and is capable of being restimulated by normal current flow, the action potential has been propagated in the forward direction only  PLATEAU IN SOME ACTION POTENTIALS: In some instances, the excited membrane does not repolarize immediately after depolarization; instead, the potential remains on a plateau near the peak of the spike potential for many milliseconds. This type of action potential occurs in heart muscle fibers. The plateau ends when the calcium - sodium channels close and permeability to potassium ions  PROPERTIES OF AN ACTION POTENTIAL: 1. All or none (nothing)Law 2. Absolute & Relative Refractory period 3. Conduction through - A myelinated nerve fiber (Saltatory conduction) - An unmyelinated nerve fiber (Point to Point Conduction) THANKYO U