Calcium-dependent potassium channels in the heart: clarity and confusion

Abstract

This editorial refers to ‘Critical roles of a small conductance Ca2+-activated K+ channel (SK3) in the repolarization process of atrial myocytes’ by X.-D. Zhang et al. , pp. 317–325, this issue and ‘Overexpression of KCNN3 results in sudden cardiac death’ by S. Mahida et al. , doi:10.1093/cvr/cvt262 and ‘Overexpression of KCNN3 results in sudden cardiac death’ by S. Mahida et al ., doi:10.1093/cvr/cvt269. Small-conductance Ca2+-activated K+ (SK) channels are widely expressed throughout the body. After initial dismissal of a functional role for SK channels in the heart,1 a series of elegant studies from the Chiamvimonvat laboratory rekindled interest,2,3 as did subsequent work suggesting that tachypaced rabbit pulmonary veins have enhanced SK channel trafficking to the cell membrane that accelerates repolarization.4 The field really got a boost from GWAS evidence, suggesting that variants in the KCNN3 gene encoding SK isoform 3 (SK3) channels are associated with the risk of atrial fibrillation (AF) in man.5 Questions remain, however, about the functional role that SK currents play in cardiac electrophysiology. Recent studies of SK channels in native tissues have provided conflicting results. Two investigations …