Cardiac action potential
Unlike the action potential in skeletal muscle cells, the cardiac action potential is not initiated by nervous activity. Instead, it arises from a group of specialized cells known as pacemaker cells, that have automatic action potential generation capability. In healthy hearts, these cells form the cardiac pacemaker and are found in the sinoatrial node in the right atrium. They produce roughly 60–100 action potentials every minute. The action potential passes along the cell membrane causing the cell to contract, therefore the activity of the sinoatrial node results in a resting heart rate of roughly 60–100 beats per minute. All cardiac muscle cells are electrically linked to one another, by intercalated discs which allow the action potential to pass from one cell to the next.[1][2] This means that all atrial cells can contract together, and then all ventricular cells.
Rate dependence of the action potential is a fundamental property of cardiac cells and alterations can lead to severe cardiac diseases including cardiac arrhythmia and sometimes sudden death.[3] Action potential activity within the heart can be recorded to produce an electrocardiogram (ECG). This is a series of upward and downward spikes (labelled P, Q, R, S and T) that represent the depolarization (voltage becoming more positive) and repolarization (voltage becoming more negative) of the action potential in the atria and ventricles.[4]
Refractory period[edit]
Cardiac cells have two refractory periods, the first from the beginning of phase 0 until part way through phase 3; this is known as the absolute refractory period during which it is impossible for the cell to produce another action potential. This is immediately followed, until the end of phase 3, by a relative refractory period, during which a stronger-than-usual stimulus is required to produce another action potential.[24][25]
These two refractory periods are caused by changes in the states of sodium and potassium channels. The rapid depolarization of the cell, during phase 0, causes the membrane potential to approach sodium's equilibrium potential (i.e. the membrane potential at which sodium is no longer drawn into or out of the cell). As the membrane potential becomes more positive, the sodium channels then close and lock, this is known as the "inactivated" state. During this state the channels cannot be opened regardless of the strength of the excitatory stimulus—this gives rise to the absolute refractory period. The relative refractory period is due to the leaking of potassium ions, which makes the membrane potential more negative (i.e. it is hyperpolarised), this resets the sodium channels; opening the inactivation gate, but still leaving the channel closed. Because some of the voltage-gated sodium ion channels have recovered and the voltage-gated potassium ion channels remain open, it is possible to initiate another action potential if the stimulus is stronger than a stimulus which can fire an action potential when the membrane is at rest.[26]
Gap junctions[edit]
Gap junctions allow the action potential to be transferred from one cell to the next (they are said to electrically couple neighbouring cardiac cells). They are made from the connexin family of proteins, that form a pore through which ions (including Na+, Ca2+ and K+) can pass. As potassium is highest within the cell, it is mainly potassium that passes through. This increased potassium in the neighbour cell causes the membrane potential to increase slightly, activating the sodium channels and initiating an action potential in this cell. (A brief chemical gradient driven efflux of Na+ through the connexon at peak depolarization causes the conduction of cell to cell depolarization, not potassium.)[27] These connections allow for the rapid conduction of the action potential throughout the heart and are responsible for allowing all of the cells in the atria to contract together as well as all of the cells in the ventricles.[28] Uncoordinated contraction of heart muscles is the basis for arrhythmia and heart failure.[29]