Properties of the large conductance K+ channel (BKCa) in skeletal muscle arterioles

Abstract

BKCa channels provide a mechanism for hyperpolarization and relaxation in arteriolar smooth muscle. Thus, BKCa is modulated by Ca2+ sparks providing a negative feedback on myogenic constriction and is a target for endothelium-dependent hyperpolarization. However, discordant results in differing vascular beds and between preparations suggest that heterogeneity may exist in these mechanisms. The present study examined properties of BKCa in rat cremaster muscle arterioles using in vivo and in vitro approaches. Under both conditions the BKCa inhibitor, iberiotoxin (IBTX, 10–7M), caused constriction of the 1st order arteriole. The voltage-gated K+ channel blocker, 4-aminopyridine similarly caused constriction while in vitro studies showed the extent of IBTX and 4-AP-induced constriction to be unaffected by level of intraluminal pressure. Whole cell patch clamp studies on dispersed 1A smooth muscle cells showed that total K+ current was inhibited by <10% by IBTX but blocked approx. 65% by 4-AP. Real-time PCR indicated a lower ratio of beta:alpha subunits compared to that seen in branches of the middle cerebral artery taken from the same animals. Collectively, the data are consistent with a background level of BKCa activity in skeletal muscle arterioles. Further, differences in relative expression of channel subunits between vascular beds suggests that regulation may also occur at the level of transcription.