Cardiac action potential

The cardiac action potential is the electrical activity of the individual cells of the electrical conduction system of the heart.

The cardiac action potential differs significantly in different portions of the heart. This differentiation of the action potentials allows the different electrical characteristics of the different portions of the heart. For instance, the specialized conduction tissue of the heart has the special property of depolarizing without any external influence. This is known as automaticity.

The electrical activity of the specialized conduction tissues are not apparent on the surface electrocardiogram (ECG). This is due to the relatively small mass of these tissues compared to the myocardium (muscle of the heart).

Resting membrane potential

**Intracellular and extracellular ion concentrations**
Ion	Extracellular concentration (mM)	Intracellular concentration	Ratio of extracellular to intracellular concentration
Na⁺	145	15 mmol/L	9.7
K⁺	4	150 mmol/L	0.027
Cl^-	120	5-30 mmol/L	4-24
Ca²⁺	2	10^-7 mmol/L	2 x 10⁴
Although intracellular Ca²⁺ content is about 2 mM, most of this is bound or sequestered in intracellular organelles (mitochondria and sarcoplasmic reticulum).

The resting membrane potential is the difference in ionic charge across the membrane of the cell during phase 4 of the action potential. The normal resting membrane potential in the ventricular myocardium is about -85 to -95 mV. This potential is determined by the selective permeability of the cell membrane to various ions. Membrane is permeable to K⁺, and is relatively impermeable to other ions. The resting membrane potential is therefore determined by the K⁺ gradient across the cell membrane (the reversal potential for K⁺). The maintenance of this electrical gradient is due to various ion pumps and exchange mechanisms, including the Na⁺-K⁺ ion exchange pump and the Na⁺-Ca²⁺ exchange mechanism.

Intracellularly (within the cell), K⁺ is the principle cation, and phosphate and the conjugate bases of organic acids are the dominant anions. Extracellularly (outside the cell), Na⁺ and Cl^- predominate.

Phases of the cardiac action potential

The standard model used to understand the cardiac action potential is the action potential of the ventricular myocyte. The action potential has 5 phases (numbered 0-4). Phase 4 is the resting membrane potential, and describes the membrane potential when the cell is not being stimulated.

Once the cell is electrically stimulated (typically by an electric current from an adjacent cell), it begins a sequence of actions involving the influx and eflux of multiple cations and anions that together produce the action potential of the cell, propogating the electrical stimulation to the cells that lie adjacent to it. In this fashion, an electrical stimulation is conducted from one cell to all the cells that are adjacent to it, to all the cells of the heart.

Phase 4

Phase 4 is the resting membrane potential. This is the period that the cell remains in until it is stimulated by an external electrical stimulus (typically an adjacent cell). This phase of the action potential is associated with diastole of the chamber of the heart.

Certain cells of the heart have the ability to undergo spontaneous depolarization, in which an action potential is generated without any influence from nearby cells. This is also known as automaticity. The cells that can undergo spontaneous depolarization the fastest are the primary pacemaker cells of the heart, and set the heart rate. Usually, these are cells in the SA node of the heart. Electrical activity that originates from the SA node is propagated to the rest of the heart. The fastest conduction of the electrical activity is via the electrical conduction system of the heart.

In cases of heart block, in which the activity of the primary pacemaker does not propagate to the rest of the heart, a latent pacemaker (also known as an escape pacemaker) will undergo spontaneous depolarization and create an action potential.

The mechanism of automaticity is still unclear. Depolarization of SA and AV nodal cells largely depend on a net increase in intracellular positive charge. Mechanisms include a decrease in the net K⁺ outward flow, and a time-dependent increase in flow of Na⁺ and Ca²⁺ ions.

Phase 0

Phase 0 is the rapid depolarization phase. The slope of phase 0 is determined by the maximum rate of depolarization of the cell and is known as V_max. This phase is due to opening of the fast Na⁺ channels and the subsequent rapid increase in the membrane conductance to Na⁺ (g_Na) and a rapid influx of ionic current in the form of Na⁺ ions (I_Na) into the cell.

The ability of the cell to open the fast Na⁺ channels during phase 0 is related to the membrane potential at the moment of excitation. If the membrane potential is at its baseline (about -85 mV), all the fast Na⁺ channels are closed, and excitation will open them all, causing a large influx of Na⁺ ions. If, however, the membrane potential is less negative, some of the fast Na⁺ channels will be opened earlier, causing a lesser response to excitation of the cell membrane and a lower V_max.

The maximal fast inward Na⁺ current is generated when the membrane potential is at the normal resting potential (-85 to –95 mV). If the resting membrane potential is reduced to a low enough level, the increase in fast inward Na⁺ current may be inadequate to produce a response, making the fiber unexcitable.

The fast Na⁺ channel

The fast sodium channel is made up of two gates, the m gate and the h gate. It is the interaction of these two gates that allows Na⁺ to enter the cell through this channel. In the resting state, the m gate is closed and the h gate is open. Upon electrical stimulation of the cell, the m gate opens quickly while simultaneously the h gate closes slowly. For a brief period of time, both gates are open and Na⁺ can enter the cell across the electrochemical gradient.

Phase 1

Phase 1 of the action potential is due to closure of the fast Na⁺ channels. The transient net outward current is due to the movement of K⁺ and Cl^- ions.

Phase 0 and 1 together correspond to the R and S waves of the ECG.

Phase 2

Phase 2 of the action potential corresponds to the ST segment of the ECG.

This "plateau" phase of the cardiac action potential is sustained by a balance between inward movement of Ca²⁺ (I_Ca) through L-type calcium channels and outward movement of K⁺ through potassium channels.

Phase 3

During phase 3 of the action potential, the K⁺ channel is still open, allowing more K⁺ to leave the cell and accumulate in the extracellular space. This net loss of positive charge causes the cell to repolarize. The k⁺ channels close when the membrane potential is restored to about -40 to -45 mV.

Phase 3 of the action potential corresponds to the T wave on the ECG.

Pacemaker potentials

Pacemaker cells are special myocardial cells, that discharge rhythmically. They have a special type of action potential, phase 4 also being called "prepotential". The first part of the prepotential is caused by relatively smaller efflux of K⁺ in the phase 4 of the action potential. Later, the transient type of the calcium channel (T channel) opens, forming the second part of the prepotential. As the potential declines to the firing level (around -40 mV), the long lasting calcium channel opens, leading to depolarization. The action potentials in these cells are mostly due to Ca²⁺, with only a little influence of Na⁺ influx. This explains the absence of a sharp depolarizing spike in action potentials of SA and AV nodes. The inward, slowly depolarizing current seen in these cells is given the designation I(f), for the 'funny' (as in strange) current.

Abnormal automaticity

The normal activity of the pacemaker cells of the heart is to spontaneously depolarize at a regular rhythm, generating the normal heart rate. Abnormal automaticity involves the abnormal spontaneous depolarization of cells of the heart. This typically causes arrhythmias (irregular rhythms) in the heart.

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