Question

In a step by step manner, explain how the voltage regulated channels produce an action potential.

Answer 1

Generation and Propagation of Action potential: The stimulation of a neuron (say, binding of a neurotransmitter) causes opening of various types of on channels. If it causes the change in membrane potential to the threshold value (-50 mV), an action potential is generated at axon hillock. The propagative unidirectional ionic current generated in axon due to induced depolarization mediated by voltage-gated Na⁺ ions is called an action potential or nerve impulse or spike.

The increase in membrane potential to the threshold potential under the influence of stimuli is termed the stimulation phase. The threshold membrane potential causes opening of some voltage-gate Na⁺ channels resulting in a rapid influx (transport of ions into the cell) of Na⁺ ions. It increases the relative [Na⁺] in cytoplasm making the membrane potential relatively more positive, the process being called depolarization. The preceding Na⁺ influx (say, influx 1) opens more voltage-gated Na⁺ channels that leads influx of more Na⁺ ions (influx 2); now influx 2 triggers the opening of more voltage-gated Na⁺ channels, and so on like a positive feedback loop. The process of successive opening of more voltage-gated Na⁺ channels under the influence of previous Na⁺ influx till attainment of peak potential is called Hodgkin cycle. As a result, the membrane potential rapidly increases from -70 mV (at resting potential) to around +40 mV (peak potential), this period of action potential is called rising phase or depolarization. It lasts for around 1 millisecond. The increase in membrane potential above 0 mV to peak potential of +40 mV (or as high as +65 mV depending on the type of cell) is called peak phase or overshoot. At peak potential, the membrane potential is nearly equal (but always a bit lesser than) to electrical potential of Na⁺ ions (i.e. V_m » E_Na+). At the peak membrane potential, the resultant positive charge in cytoplasm triggers spontaneous inactivation of voltage-gated Na⁺ channels simultaneously with opening of voltage-gated K⁺ channels.

The rate of activation (opening) of voltage-gated K⁺ channels is relatively slower than that of voltage-gated Na⁺ channels because of Hodgkin cycle phenomenon is coupled to Na⁺ influx only but not with K⁺ efflux. Therefore, voltage-gated K⁺ channels are also called delayed rectifiers. Opening of voltage-gated K⁺ channels (while voltage-gated Na⁺ channels remain closed) facilitate rapid efflux (transport of ions outside cell) of positively charged K⁺ ions from cytoplasm to ECM. The gradual loss of [K⁺] from cytoplasm decrease the membrane potential from +40 mV (peak potential) to -70 mV (resting potential)- the process being called repolarization. At is stage, the membrane potential is nearly equal to electrical potential of K⁺ ions (i.e. V_m = E_k+ = -70 mV). The period of lowering to membrane potential from peak to resting potential (-70 mV) is called falling phase.

Unlike voltage-gated Na⁺ channels which all (almost) close at V_m = E_Na+ (peak phase), not all voltage-gated K⁺ channels close at V_m= E_K+. Moreover, the influx of Ca²⁺ ions during depolarization phase, also triggers opening of some more voltage-gated K⁺ channels. Altogether, the opened K⁺ efflux more positively charged K⁺ ions outside cell, further lowering the membrane potential to around -80 mV. The lowering of membrane potential below resting potential is called hyperpolarization or more precisely afterhyperpolarization. This highly negative membrane potential (- 80 mV) causes closure of almost all voltage-gated K⁺ as well as Na⁺ channels.

The resting membrane potential is restored from -80 mV to normal resting potential of -70 mV by the action of Na⁺-K⁺ pump (while most of voltage-gated K⁺ and Na⁺ channels remain closed) on expenditure of metabolic energy. This period of restoration of resting membrane potential is called returning phase.