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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., pp. 326–334, this issue.

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 using apamin to block SK currents showed increased action potential duration (APD) of atrial cells,6,7 while one did not observe an effect.8 Recent detailed studies with a novel selective SK channel blocker provide insight into this variability, by showing that the expression of SK current in the canine atrium is regionally determined and increased by AF-related remodelling, such that statistically non-significant APD effects of SK channel block are seen in control left-atrium, with larger statistically significant effects in pulmonary vein cardiomyocyte sleeves and still larger effects in the presence of AF-related remodelling.9 There are also discrepant findings regarding the effects of SK blockade on atrial arrhythmias: several studies have shown clear anti-arrhyhmic actions,9–11 while one paper reported pro-arrhythmic effects.6

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Editorial
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