<unk>  increases the risk of abnormal heart rhythms by disturbing the electrical signals that are used to coordinate individual heart cells. The genetic mutation disturbs an ion channel responsible for the flow of potassium, reducing the /K1 current. This prolongs of the cardiac action potential<unk>  the characteristic pattern of voltage changes across the cell membrane that occur with each heart beat, and depolarises the resting membrane potential of cardiac and skeletal muscle cells. Cardiac and skeletal muscle cells, when relaxed, have fewer positively charged ions on the inner side of their cell membrane than on the outer side, referred to as their membranes being polarised. The main ion current responsible for maintaining this polarity is /K1, and a decrease in this current leads to less polarity at rest, or a depolarised resting membrane potential. When these cells contract, positively charged ions such as sodium and calcium enter the cell through ion channels, depolarising or reversing this polarity. After a contraction has taken place, the cell restores its polarity (or repolarises) by allowing positively charged ions such as potassium to leave the cell, restoring the membrane to its relaxed, polarised state. The genetic mutation found in those with<unk><unk><unk>  decreases the flow of potassium, slowing the rate of repolarisation which can be seen in individual cardiac muscle cells as a longer action potential and on the surface ECG as a prolonged QT interval. Mechanisms underlying early afterdepolarisations (EADs) and delayed afterdepolarisations (DADs) responsible for the arrhythmias seen in<unk>  The prolonged action potentials can lead to arrhythmias through several potential mechanisms. The frequent ventricular ectopy and bidirectional VT typical of<unk>  are initiated by a triggering beat in the form of an afterdepolarisation. Early afterdepolarisations, occurring before the cell has fully repolarised, arise due to reactivation of calcium and sodium channels that would normally be inactivated until the next heartbeat is due. Under the right conditions, reactivation of these currents can cause further depolarisation of the cell, facilitated by the sodium-calcium exchanger. Early afterdepolarisations may occur as single events, but may occur repeatedly leading to multiple rapid activations of the cell. Delayed afterdepolarisations, occurring after repolarisation has completed, arise from the spontaneous release of calcium from the intracellular calcium store known as the sarcoplasmic reticulum. This calcium release then leaves the cell through the sodium calcium exchanger in exchange for sodium, generating a net inward current and depolarising the cell membrane. If this transient inward current is large enough, a premature action potential is triggered. The muscle weakness seen in those with<unk>  arises from the depolarisation of the resting membrane potential caused by a decrease in /K1. The depolarised resting membrane potential means that sodium channels which are responsible for initiating action potentials are unable to fully recover from inactivation, leading to a less excitable membrane and less forceful muscle contraction. The mechanisms underlying the skeletal abnormalities seen in<unk>  have not been fully explained. Possibilities include impaired function of osteoclasts, cells which regulate bone growth, or disruption of the bone morphogenetic protein signalling cascade.
Andersen–Tawil syndrome
Jervell and Lange-Nielsen syndrome
Dennie–Marfan syndrome
Romano–Ward syndrome
Timothy syndrome
Marfan syndrome
Catecholaminergic polymorphic ventricular tachycardia
CAMFAK syndrome