Decreased expression of small-conductance Ca2+-activated K+ channels SK1 and SK2 in human chronic atrial fibrillation

Aims: Small-conductance Ca2+-activated K+ (SK) channels are recognized as new ion channel candidates in atrial fibrillation (AF), with pivotal implications as novel drug targets due to their atrial-selective distribution in humans. The purpose of this study was to investigate whether SK channels and the Ca2+-activated K+ current (I-K,I-Ca) are involved in electrical remodeling of human chronic AF (cAF) and whether they display the differential distribution between the right (RA) and left atria (LA). Main methods: The right (RAA) and left atrial appendage (LAA) myocytes were obtained from 29 sinus rhythm (SR) and 22 cAF patients. The I-K,I-Ca and action potential (AP) were recorded using the patch-clamp technique. Three SK channel subtypes (SK1-3) expressions were assayed by western blot and real-time quantitative PCR analysis. Key findings: The I-K,I-Ca was decreased and its role in AP repolarization was attenuated in cAF, concomitant with a significant decrease in protein and mRNA levels of SK1 and SK2. In either SR or cAF, there was no difference in the I-K,I-Ca density and protein and mRNA expression levels of SK1-3 between RAA and LAA myocytes. Significance: Our results demonstrated that SKI and SK2 are involved in electrical remodeling of cAF. SK1-3 and I-K,I-Ca do not display the inter-atrial differential distribution in SR or cAF. These findings provide a new insight into mechanisms of electrical remodeling of human cAF. (c) 2011 Elsevier Inc. All rights reserved.