Calcium-activated potassium channels contribute to human skeletal muscle microvascular endothelial dysfunction related to cardiopulmonary bypass

Background. We investigated the role of calcium-activated potassium (K-Ca) channel activity in human skeletal muscle microvascular function in the setting of cardiopulmonary bypass (CPB). Methods and Results. Human skeletal muscle arterioles (80- to 180 mu m in diameter) were dissected from tissue harvested before and after CPB. In vitro relaxation responses of precontracted arterioles in a pressurized no-flow state were examined in the presence of K-Ca channel activators/blockers and several other vasodilators. Post-CPB responses, to the activator of intermediate (IKCa) and small conductance (SKCa) K-Ca channels, NS309, to the endothelium-dependent vasodilator adenosine 5'-diphosphate (ADP), and to substance P were reduced compared with pre-CPB responses (P < .05), respectively, whereas responses to the activator of large conductance (BKCa,) K-Ca channels, NS1619, and to the endothelium-independent, vasodilator, sodium nitroprusside (SNP) were unchanged. Endothelial denudation decreased NS309-induced relaxation and abolished that induced by ADP or substance P (P < .05), but had no effect on relaxation induced by either NS1619 or SNP. Polypeptide levels of BKCa, IKCa, and SK3(Ca) were not altered post-CPB. Conclusion. IK/SK-mediated relaxation is predominantly endothelium dependent, whereas BK-mediated relaxation seems lobe largely independent of endothelial function in human skeletal muscle microvasculature. CPB-associated microvascular dysfunction likely arises in part from impaired function of endothelial SK and IK channels in the peripheral mirrovasculature.