Cardiac action potential
In healthy hearts, these cells form the cardiac pacemaker and are found in the sinoatrial node in the right atrium.
[6] The action potential begins with the voltage becoming more positive; this is known as depolarization and is mainly due to the opening of sodium channels that allow Na+ to flow into the cell.
The first is to maintain the existence of the resting membrane potential by countering the depolarisation due to the leakage of ions not at the electrochemical equilibrium (e.g. sodium and calcium).
The second purpose, intricately linked to the first, is to keep the intracellular concentration more or less constant, and in this case to re-establish the original chemical gradients, that is to force the sodium and calcium which previously flowed into the cell out of it, and the potassium which previously flowed out of the cell back into it (though as the potassium is mostly at the electrochemical equilibrium, its chemical gradient will naturally reequilibrate itself opposite to the electrical gradient, without the need for an active transport mechanism).
These channels open at very negative voltages (i.e. immediately after phase 3 of the previous action potential; see below) and allow the passage of both K+ and Na+ into the cell.
Due to their unusual property of being activated by very negative membrane potentials, the movement of ions through the HCN channels is referred to as the funny current (see below).
If this increased voltage reaches the threshold potential (approximately −70 mV) it causes the Na+ channels to open.
This produces a larger influx of sodium into the cell, rapidly increasing the voltage further to around +50 mV,[6] i.e. towards the Na+ equilibrium potential.
During this phase delayed rectifier potassium channels (Iks) allow potassium to leave the cell while L-type calcium channels (activated by the influx of sodium during phase 0) allow the movement of calcium ions into the cell.
[21][11] This phase is responsible for the large duration of the action potential and is important in preventing irregular heartbeat (cardiac arrhythmia).
This ensures a net outward positive current, corresponding to negative change in membrane potential, thus allowing more types of K+ channels to open.
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.
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.
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.
These poorly selective, cation (positively charged ions) channels conduct more current as the membrane potential becomes more negative (hyperpolarised).
Sympathetic nerves directly affect these channels, resulting in an increased heart rate (see below).
[35][14] These sodium channels are voltage-dependent, opening rapidly due to depolarization of the membrane, which usually occurs from neighboring cells, through gap junctions.
They allow for a rapid flow of sodium into the cell, depolarizing the membrane completely and initiating an action potential.
Due to the rapid influx sodium ions (steep phase 0 in action potential waveform) activation and inactivation of these channels happens almost at exactly the same time.
[citation needed] Inwardly rectifying potassium channels (Kir) favour the flow of K+ into the cell.
Therefore, Kir is responsible for maintaining the resting membrane potential and initiating the depolarization phase.
This outward flow of potassium ions at the more positive membrane potentials means that the Kir can also aid the final stages of repolarisation.
[citation needed] In addition to the SAN, the AVN and Purkinje fibres also have pacemaker activity and can therefore spontaneously generate an action potential.
Sustained training of athletes causes a cardiac adaptation where the resting SAN rate is lower (sometimes around 40 beats per minute).
This leads to uncoordinated contractions between the atria and ventricles, without the correct delay in between and in severe cases can result in sudden death.
[42] The speed of action potential production in pacemaker cells is affected, but not controlled by the autonomic nervous system.
The sympathetic nervous system (nerves dominant during the body's fight-or-flight response) increase heart rate (positive chronotropy), by decreasing the time to produce an action potential in the SAN.
[43] The parasympathetic nervous system (nerves dominant while the body is resting and digesting) decreases heart rate (negative chronotropy), by increasing the time taken to produce an action potential in the SAN.
[44] The Gi-protein also inhibits the cAMP pathway therefore reducing the sympathetic effects caused by the spinal nerves.
