The Cardiac Ion Channels

Action potentials are mediated by transient changes in ion conductance across the cell surface membrane. These changes in conductance are primarily mediated by ion channels. Ion channels are membrane-embedded proteins that selectively pass specific ions upon opening. Some ion channels are constitutively open; however, most channels open following stimulation, such as through voltage changes, intracellular messengers, neurotransmitters, or shear stress. In the heart, voltage gated ion channels, conducting sodium, calcium and potassium ions, are primarily important in generating and shaping the action potential as well as exchangers and pumps that contribute to ion fluxes. The most prominent features of the cardiac action potential is the synchronised depolarisation of all the cardiomyocytes and the very long lasting depolarisation period, which in humans lasts 200-450 ms, depending on the beating frequency. The electrical impulse is generated in the pacemaker cells in the sinoatrial node located at the junction of the superior vena cava and right atrium. The electrical signal spreads to the right and left atria, thereby initiating muscular contraction and resulting in additional filling of the ventricles. When the depolarisation reaches the atrioventricular node, conduction is slowed before the depolarisation progresses to the ventricular cardiomyocytes. The electrical impulse is spread to the ventricles through a specialised conduction system formed by the His bundle branches and the Purkinje fibres, resulting in the depolarisation of the ventricular cardiomyocytes within a relatively short time span. The very long cardiac action potential mediates a long lasting increase in cytosolic calcium and, thereby, a long lasting contraction. Furthermore, the long action potential duration makes the myocardium refractory, whereby under normal physiological conditions no new action potentials will disturb the ongoing contraction. After the depolarisation phase and the plateau phase, the myocardium repolarises such that the contraction cesses and the ventricular chambers can be refilled. Disturbances in this highly fine-tuned electricalcontraction pattern termed arrhythmia can be detrimental since unorganised electrical impulse propagation in the musculature will lead to uncoordinated muscle contraction and therefore a loss of pumping function (Jespersen, 2011). The cardiac action potential is the summarised output of several different types of ion channels. The functional significance of the different ion channels depends on both the subcardial location and the biophysical configuration of the channels, as well as the