Maxi-K channel (BKCa) activity veils the myogenic tone of mesenteric artery in rats

Abstract

Arterioles and small arteries change their tone in response to transmural pressure changes, called myogenic tone (MT). In comparison to the branches of cerebral arteries (CA) showing prominent MT, the third branches of mesenteric arteries (MA) with similar diameters show weaker MT. Here, we aimed to analyze the electrophysiological differences responsible for the weaker MT in MA (MTMA) than MT in CA (MTCA). We measured ionic current using patch clamp in isolated MA smooth muscle cells (MASMCs) and CA smooth muscle cells (CASMCs) of rats. MT was analyzed using video analysis of pressurized small arteries. Quantitative-PCR (q-PCR) and immunofluorescence confocal microscopy were used to compare the mRNA and protein expression level of big-conductance Ca2+-activated K+ channel (BKCa) subunits (Slo1 and Slo1). Whole-cell patch clamp study revealed higher density of voltage-operated Ca2+ channel current (I-CaV) in the MASMCs than in CASMCs. Although voltage-gated K+ channel current (I-Kv) was also higher in MASMCs, treatment with Kv inhibitor (4-aminopyridine) did not affect MTMA. Interestingly, BKCa current density and the frequency of spontaneous transient outward currents (STOCs) were consistently higher in MASMCs than in CASMCs. Inside-out patch clamp showed that the Ca2+-sensitivity of BKCa is higher in MASMCs than in CASMCs. Iberiotoxin, a selective BKCa inhibitor, augmented MTMA by a larger extent than MTCA. Although q-PCR analysis did not reveal a significant difference of mRNAs for Slo1 and Slo1, immunofluorescence image suggested higher expression of Slo1 in MASMCs than in CASMCs. Despite the large I-CaV density, the high activities of BKCa including the more frequent STOCs in MASMCs veils the potentially strong MTMA.