Mechanism of Dopamine-mediated Activation of Bk Channels in Human Coronary Artery Smooth Muscle Cells

Coronary artery disease (CAD) is an important cause of morbidity and mortality worldwide and is associated with a sustained increase in vascular tone. Large conductance, voltage-dependent and calcium-activated potassium (K) channels, or BK channels determine membrane electrical activity in human coronary artery smooth muscle cells (HCASMCs). Their activation leads to hyperpolarization, a decrease in coronary vascular tone and vasorelaxation. Dopamine, via the D1-like receptors, activates K channels, and may play a role in CAD. Dopamine has been shown to activate BK channels or ATP-sensitive K channels in previous studies in porcine coronary myocytes. The effects of dopamine receptor activation on K channels in human coronary artery smooth muscle cells (HCASMCs) are not known. Further, there are two D1-like receptors, D1R and D5R. We hypothesize that the specific D1-