Ionic changes in action potential manan shah First year MBBS
Learning objectives: Introduction Action potential Phases - Depolarization, Repolarization After Depolarization, After Hyperpolarization Hodgkin’s cycle Positive Feedback Negative Feedback
introduction Nerve and muscle are excitable tissues. They can undergo rapid changes in their membrane potentials. These resting potentials get converted into electrical signals that aid in cellular communications. These signalling events are mediated by ion channels. 3 of 51
Resting membrane potential RMP is the potential difference which exist across the cell membrane under resting conditions. Interior of the cell is negatively charged in relation to the exterior. The magnitude of membrane potential varies from cell to cell according to its functional status. Nerve cell has a membrane potential of -70 mV at rest, but when it gets excited the membrane potential becomes approximately +30 mV . The membrane potential which is measured when the cell is excited is called action potential.
Action potential An action potential, also known as impulse or spike potential is a rapid change in the membrane potential when a threshold stimulus is applied followed by a return back to the resting membrane potential. An action potential is conducted with the same shape and size throughout the length of a cell. The signal-carrying ability of nerve cells is due to action potential. Voltage-dependent and ligand-gated ion channel proteins in the plasma membrane are responsible for action potential.
The action potential may be defined as the sequence of changes which occur in RMP. When the stimulus is subthreshold, it does not generate action potential, but it carry out some changes in the RMP. There is depolarization of small extent for approximately 7 mV which cannot be propagated, because propagation starts only if the depolarization reaches a boosting level of 15 mV. Once the boosting level is reached, action potential occurs. The action potential basically takes place in two stages - depolarization and repolarization. When the nerve cell is excited, the polarized state (- 70 mV) is altered,
i.e. the RMP is abolished and the polarity of the nerve is reversed, i.e., interior becomes positive (+35 mV) as compared to the exterior. This is called depolarization phase . Within very short period of time back to the nearly original potential occurs and the second phase of action potential occurs called as repolarization phase. We get action potential curve when RMP is being recorded on a CRO and the nerve fibre is stimulated at a short distance from the recording electrode, which has following components : 1. RMP is marked as a straight baseline at - 70 mV. 2. Stimulus artefact is found as a low deflection of the baseline just after the stimulus is applied. The stimulus artefact happens because of the leakage of current from the stimulating electrode to the measuring electrode.
3. Latent period is recorded as a short electric period (0.5-1 ms) after the stimulus artefact. It reflects the interval between the application of stimulus and the application of action potential. 4. Firing level : On completion of latent period, phase of depolarization starts. Depolarization moves further relatively slow upto a level called the firing level (-55 mV) , at which depolarization occurs very rapidly. 5. Overshoot: After the firing level, the curve reaches the zero potential (0 mV) rapidly and then overshoots the zero line upto +35 mV.
6. Spike potential: After reaching the peak (+35 mV), the phase of depolarization is completed and the phase of repolarization starts, and the potential descends quickly near the firing level. The stage of sudden decrease of potential in depolarization and a rapid fall during repolarization phase, combinedly constitute the spike potential . Its time period is approximately 1 ms in an axon. 7. After depolarization phase is the slow repolarization phase which follows a rapid decrease in spike potential and rises up to attainment of the RMP level. It lasts for approximately 4 ms . 8. After hyperpolarization: After reaching the resting level (-70 mV) the potential further decreases and becomes more -ve (-72 mV). This phase is called after hyperpolarization . It lasts for a prolonged period (35-40 ms). Finally, the RMP is restored.
Opening and Closure of Gates during A.P. : Resting state During Depolarization Peak of action potential Peak of action potential Later part of repolarization Later part of repolarization
positive feedback Positive feedback Na+ channels exert +ve feedback Depolarizing stimulus Opening of voltage-gated Na+ channels Inactivation of Na+ channels Depolarization of membrane potential Increased flow of Na+ into the cell Increased P Na Stop Start
Hodgkin’s cycle The opening of certain Na + channels leads to further opening of remaining Na + channels This is an example of positive feedback control in which a stimulus triggering an event further facilitates the process.
negative feedback Negative feedback K+ channels exert -ve feedback Start Depolarization of membrane by Na+ influx Opening of voltage-gated K+ channels Increased P K+ Increased flow of K+ out of the cell Repolarization of membrane potential
Clinical aspect Local Anesthetics : Among the most important stabilizers are the many substances used clinically as local anesthetics, including procaine and tetracaine. Most of these agents act directly on the activation gates of the sodium channels, making it much more difficult for these gates to open and thereby reducing membrane excitability. When excitability has been reduced so low that the ratio of action potential strength to excitability threshold (called the safety factor) is reduced below 1.0 , nerve impulses fail to pass along the anesthetized nerves