Large Conductance Calcium-Activated Potassium Channels Contribute to the Reduced Myogenic Tone of Peripheral Microvasculature After Cardiopulmonary Bypass

Abstract

We investigated the role of calcium-activated potassium (K(Ca)) channel activation in myogenic tone in human peripheral microvasculature after heart surgery. Human skeletal muscle arterioles (90-180microm diameter) were dissected from tissue harvested pre- and post-cardiopulmonary bypass (CPB) during cardiac surgery. Myogenic reactivity in response to stepwise increases in intraluminal pressure was studied between pressure steps. Microvessel tone was determined pre-CPB, post-CPB, and after blockade of K(Ca) channels. Expression and localization of large conductance (BK) K(Ca) channels in the coronary microvasculature was assessed by immunoblot and immunofluorescence photomicroscopy. Myogenic tone of skeletal muscle arterioles was significantly reduced post-CPB compared with pre-CPB. Decrease in myogenic tone after CPB was reflected by the increase in microvessel internal diameter. Myogenic tone of post-CPB microvessels was significantly increased after treatment with BK(Ca)-blocker iberiotoxin, but unchanged in the combined presence of the blockers of intermediate (IK(Ca)) and small conductance (SK(Ca)) K(Ca) channels, TRAM34/apamin. The increases in myogenic tone after iberiotoxin treatment were demonstrated as a decrease in microvessel internal diameter. No significant differences in BK(Ca) protein levels were noted comparing pre- and post-CPB conditions judged by immunoblot and by immunofluorescence staining of skeletal muscle microvessels. Prominent staining for BK(Ca)-alpha and BK(Ca)-beta(1) subunits localized to the microvascular smooth muscle. CPB-associated decrease in peripheral myogenic reactivity is likely due to activation of BK(Ca), but not IK(Ca) or SK(Ca). CPB may increase BK(Ca) activity without increasing BK polypeptide level.