Maxi-K channel (BK_{C a} ) 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 (BKC a) subunits (Slo1α and Sloβ1). Whole‐cell patch clamp study revealed higher density of voltage‐operated Ca2+ channel current (IC aV) in the MASMCs than in CASMCs. Although voltage‐gated K+ channel current (IK v) was also higher in MASMCs, treatment with Kv inhibitor (4‐aminopyridine) did not affect MTMA. Interestingly, BKC a 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 BKC a is higher in MASMCs than in CASMCs. Iberiotoxin, a selective BKC a inhibitor, augmented MTMA by a larger extent than MTCA. Although q‐PCR analysis did not reveal a significant difference of mRNAs for Slo1α and Sloβ1, immunofluorescence image suggested higher expression of Slo1α in MASMCs than in CASMCs. Despite the large IC aV density, the high activities of BKC a including the more frequent STOCs in MASMCs veils the potentially strong MTMA.

Endurance exercise training restores atrophy-induced decreases of myogenic response and ionic currents in rat skeletal muscle artery

“…Here, we used unilateral sciatic denervation model rats to investigate the MRs and ionic currents of arteries feeding the lower hindlimb muscles. Although the DFAs used in this study were feeding arteries with relatively smaller diameter rather than intramuscular arterioles, the rat DFAs consistently showed MRs under a wide range of pressures, as demonstrated in our previous study (29). The atrophic side DFAs of 5w rats exhibited poor MRs and depressed ionic currents in myocytes.…”

“…Interestingly, previous studies on I BKCa show that (as opposed to other K ϩ channel currents) it exhibits increased current density under pathological conditions such as hypertension and that exercise training reverses this (18,26,34). Because the contribution of BK Ca to setting the basal contractility and MR are different between artery types, further investigations might reveal actual increases in I BKCa in the vessels perfusing disused tissue (29).…”