Role of Small-Conductance Calcium-Activated Potassium Channels in Atrial Electrophysiology and Fibrillation in the Dog

Abstract

+ , Ca 2+, or other K + currents. Whole-cell SK current sensitive to NS8593 was significantly larger in pulmonary vein (PV) versus left atrial (LA) cells, without a difference in SK single-channel open probability (P o ), whereas AT-P enhanced both whole-cell SK currents and single-channel P o . SK-current block increased action potential duration in both PV and LA cells after AT-P; but only in PV cells in absence of AT-P. SK2 expression was more abundant at both mRNA and protein levels for PV versus LA in control dogs, in both control and AT-P; AT-P upregulated only SK1 at the protein level. Intravenous administration of NS8593 (5 mg/kg) significantly prolonged atrial refractoriness and reduced AF duration without affecting the Wenckebach cycle length, left ventricular refractoriness, or blood pressure. Conclusions-SK

Mechanisms underlying the cardiac pacemaker: the role of SK4 calcium-activated potassium channels

“…They mediate the afterhyperpolarization, which ends the action potential [142] . In the periphery, the SK channels are expressed in T-lymphocytes and atrial cells and play an important role in atrial repolarization [143][144][145][146][147][148] . SK1 channels are resistant to apamin [136] , and their unitary conductance varies from 11 to 26 pS depending on the experimental conditions [149][150][151] .…”

“…The knockout of the SK2 channels leads to a decrease in the firing rate of the AVN cells, whereas the overexpression of the channel is accompanied by shorter APs with increased frequency [147] . SK2 channels are also thought to maintain atrial fibrillation [148] . Apamin, a selective SK2 blocker, delays AP repolarization by elongating the APD 50 in isolated mouse AVN and atrial cells at concentrations from 50 to 500 pmol/L [146,147] .…”

Ca²⁺-Activated K⁺ Channels as Therapeutic Targets for Myocardial and Vascular Protection

“…21,23,24 SKCa subtypes exhibit differential distribution in the heart. Tuteja et al showed that in the mouse heart expression levels of SK1 and SK2 are approximately 50% higher in the atria than in the ventricles, while SK3 levels are similar.…”

KCNN3 SNP rs13376333 on Chromosome 1q21 Confers Increased Risk of Atrial Fibrillation

“…23) Subsequently, another study showed that AF risk could be reduced by SK channel inhibition, and animal studies revealed that inhibition of SK channel could prolong the atrial effective refractory period. [24][25][26] A more recent study demonstrated that SK3 channels were overexpressed in atrial myocytes from SK3 T/T mutant mice. Using patch-clamp techniques, they further showed that the mutant mice had a shortened action potential during repolarization compared to the wild type mice.…”