Structure and function of the cardiac sodium channels

The coincident cloning of the voltage-gated Na channel from the electric ee l electroplax and development of patch-clamp methodology has allowed an exp losive phase of investigation into the structural basis of cardiac Na chann el function. Recognizing the importance of structural motifs that underlie gating (charged S4 segments, III-IV linker) and permeation (P-loops) have c omplemented new molecular information surrounding inherited cardiac arrhyth mias, such as the chromosome 3-linked form of the long QT syndrome. Althoug h the proarrhythmic potential recognized in the CAST trial [1] slowed the d evelopment of class I antiarrhythmic agents, our emerging understanding of the molecular pharmacology of Na channels may motivate strategies for Na-ch annel drug discovery that involve targeting particular structural domains. (C) 1999 Elsevier Science BN. All rights reserved.