Inherited sodium channelopathies: Novel therapeutic and proarrhythmic molecular mechanisms

Voltage-gated sodium (Na) channels, transmembrane proteins that produce the ionic current responsible for the rapid upstroke of the cardiac action pot ential, are key elements required for rapid conduction through the myocardi um and maintenance of the cardiac rhythm. The exquisite sensitivity of the cardiac rhythm to Na channel function is manifest in the proarrhythmic comp lications of "antiarrhythmic" Na channel blockade in patients with myocardi al ischemia. More recently studies of inherited single amino acid substitut ions in Na channels have unveiled a remarkable array of cardiac rhythm dist urbances, as well as surprising pharmacologic sensitivities. Hence, the sod ium channelopathies are providing new molecular insights into mechanisms wh ereby altered ion channel behavior precipitates cardiac arrhythmias. (C) 20 01, Elsevier Science Inc.