Down-regulation of the Small Conductance Calcium-activated Potassium Channels in Diabetic Mouse Atria

Abstract

Background: SK channels are implicated in atrial fibrillation (AF), and diabetes (DM) is a risk factor for AF. Results: Atrial SK2 and SK3 are significantly down-regulated from accelerated turnover in diabetic mice, resulting in action potential prolongation and arrhythmias. Conclusion: SK channel down-regulation may lead to arrhythmogenesis. Significance: SK channel down-regulation contributes to atrial electrophysiological dysfunction in DM.

Direct effect of chronic hypoxia in suppressing large conductance Ca2+‐activated K+ channel activity in ovine uterine arteries via increasing oxidative stress

“…These observations support the notion that ROS play an important causative role in chronic hypoxia-induced BK Ca channel repression and dysfunction in uterine arteries. Consistent with the present findings, oxidative stress was attributed to down-regulation of the BK Ca channel β1 subunit in arteries, as well as SK Ca and IK Ca channels in atria of diabetic rodents (Lu et al 2012;Zhao et al 2014;Yi et al 2015). Taken together, these studies provide evidence that the direct effect of chronic hypoxia regulates BK Ca channel function in uterine arteries of pregnant animals via increased oxidative stress, involving both post-translational modification and gene expression.…”

“…Our recent studies demonstrated that long-term high-altitude hypoxia during gestation increased ROS production in ovine uterine arteries, in part due to increased expression and activity of Nox2 . It has been shown that ROS are implicated in down-regulating BK Ca channels, as well as small (SK Ca ) and intermediate (IK Ca ) conductance Ca 2+ -activated K + channels in the cardiovascular system (Lu et al 2012;Zhao et al 2014;Yi et al 2015). Herein, we present novel evidence that prolonged hypoxia has a direct effect in inhibiting the BK Ca channel activity in uterine arteries by increasing oxidative stress.…”

“…; Yi et al . ). Taken together, these studies provide evidence that the direct effect of chronic hypoxia regulates BK Ca channel function in uterine arteries of pregnant animals via increased oxidative stress, involving both post‐translational modification and gene expression.…”

“…; Yi et al . ). Herein, we present novel evidence that prolonged hypoxia has a direct effect in inhibiting the BK Ca channel activity in uterine arteries by increasing oxidative stress.…”

KCNN2 polymorphisms and cardiac tachyarrhythmias

“…[7–9] The SK current is downregulated in diabetic mouse atria and in human chronic atrial fibrillation (AF). [10,11] Inhibition of SK current is proarrhythmic in healthy atria but antiarrhythmic in atrial tachypacing-induced remodeled atria due to the associated increase in action potential duration. [12–15] Although SK current is either very small or undetectable in normal ventricular myocytes paced at normal rates, [16–18] it is important for ventricular repolarization in normal hearts with bradycardia and/or hypokalemia, as well as in ischemic and failing ventricles.…”