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 (IK,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 IK,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 IK,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 IK,Ca density and protein and mRNA expression levels of SK1-3 between RAA and LAA myocytes. SIGNIFICANCE: Our results demonstrated that SK1 and SK2 are involved in electrical remodeling of cAF. SK1-3 and IK,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.
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 (IK,Ca) are involved in electrical remodeling of humanchronic 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 cAFpatients. The IK,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 IK,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 IK,Ca density and protein and mRNA expression levels of SK1-3 between RAA and LAA myocytes. SIGNIFICANCE: Our results demonstrated that SK1 and SK2 are involved in electrical remodeling of cAF. SK1-3 and IK,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 humancAF.
Authors: Tesfaye Negash Asfaw; Leonid Tyan; Alexey V Glukhov; Vladimir E Bondarenko Journal: Am J Physiol Heart Circ Physiol Date: 2020-01-17 Impact factor: 4.733
Authors: Ann-Kathrin Rahm; Teresa Wieder; Dominik Gramlich; Mara Elena Müller; Maximilian N Wunsch; Fadwa A El Tahry; Tanja Heimberger; Steffi Sandke; Tanja Weis; Patrick Most; Hugo A Katus; Dierk Thomas; Patrick Lugenbiel Journal: Physiol Rep Date: 2021-06
Authors: Ann-Kathrin Rahm; Dominik Gramlich; Teresa Wieder; Mara Elena Müller; Axel Schoeffel; Fadwa A El Tahry; Patrick Most; Tanja Heimberger; Steffi Sandke; Tanja Weis; Nina D Ullrich; Thomas Korff; Patrick Lugenbiel; Hugo A Katus; Dierk Thomas Journal: Pharmgenomics Pers Med Date: 2021-05-20