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 potential, are key elements required for rapid conduction through the myocardium and maintenance of the cardiac rhythm. The exquisite sensitivity of the cardiac rhythm to Na channel function is manifest in the proarrhythmic complications of "antiarrhythmic" Na channel blockade in patients with myocardial ischemia. More recently, studies of inherited single amino acid substitutions in Na channels have unveiled a remarkable array of cardiac rhythm disturbances, as well as surprising pharmacologic sensitivities. Hence, the sodium channelopathies are providing new molecular insights into mechanisms whereby altered ion channel behavior precipitates cardiac arrhythmias.
Balser
J R
JR
Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN 37232-6602, USA. jeff.balser@mcmail.vanderbilt.edu
D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008133:Long QT Syndrome / Q000235:genetics; D026941:Sodium Channel Blockers / Q000627:therapeutic use; D015222:Sodium Channels / Q000235:genetics / Q000502:physiology
D026941:Sodium Channel Blockers; D015222:Sodium Channels