Potassium channels and regulation of the microcirculation.

Potassium channels represent the dominant ion conductance of vascular smooth muscle cell membranes and play a major role in the regulation of membrane potential (18,19). Membrane potential, in turn, regulates the open state probability of voltage-gated Ca channels (18,19). Thus, as illustrated in Fig. 1, the closure of K channels and the loss of outward K current lead to depolarization, opening of Ca channels, Ca influx, and constriction. Conversely, the opening of K channels causes hyperpolarization, the closure of Ca channels, and vasodilation. Studies of vascular smooth muscle cells from large arteries have identified at least five different classes of K channels present in the sarcolemma of these cells, including adenosine triphosphate (ATP)sensitive K (KATP) channels (19); large-conductance, Ca-activated K (KCa) channels (19); small-conductance, Ca-activated K (KS) channels (9); voltage-sensitive K (KV) (19); and inward rectifier K (KIR) channels (19). However, we are only now beginning to explore which of these channels are expressed in different microcirculations and to evaluate the roles played by various K channels in the regulation of microvascular function. In this review I focus on three K channels that we have identified in vascular muscle cells isolated from secondand third-order cremasteric arterioles: (1) ATP-sensitive K (KATP) channels inhibited by the sulfonylurea, glibenclamide; (2) large-conductance, Ca-activated K (KCa) channels inhibited by the scorpion toxin, iberiotoxin, or millimolar concentrations of tetraethyl ammonium (TEA); and (3) voltage-sensitive K (KV) channels inhibited by 4aminopyridine.