Exp Clin Cardiol. 2003;8(3):119-24.
Experimental and clinical cardiology
Bernard Swynghedauw, Gaele Aubert
PMID: 19641702 PMCID: PMC2716271
This review analyzes recent data concerning the molecular determinants of repolarization time (RT) in normal and disease conditions. Considerations concerning the prognostic significance of RT were excluded. On a single normal cell, the duration of the action potential is the result of a balance between different ion currents. In vivo or on a multicellular preparation, the QT duration is modified by different transmural gradients, including the endo/epicardial gradient and the apex/base gradient. Spatial heterogeneity of the RT is not reflected by the range of the body surface QT dispersion. Inherited long QT syndrome is due to a gain or loss of function mutations located on the sodium current, the rapidly activating component of the delayed rectifier (I(Kr)) and the slowly activating component of the delayed rectifier. So far, no mutations have been detected on the transient outward K(+) current (I(tO)). Drug-induced long QT is caused by drugs that act as potassium blockers, which interact on specific domains of K(+) channel subunits, mainly on I(Kr). Several drugs may reveal 'forme frustes' of an inherited long QT. A prolonged RT is a well documented finding in cardiac hypertrophy and heart failure and is mostly caused by the noninduction and corresponding decreased density of the K(+) channel responsible for I(tO). Hypertrophy can even reverse the trans-mural gradient. In humans and rats, isolated pressure overload prolongs the QT interval. The reduction in I(tO) is likely to participate in the slowing of the cardiac cycle and reflects the re-expression of the fetal programme.
Keywords: Cardiac genetics; Cardiac hypertrophy; Ion channels; Long QT; Sudden death
