High Activity of Large‐conductance Ca 2+ ‐activated K + channels Underlies Weak Myogenic Tone of Rat Mesenteric Arteries in Comparison of Cerebral Artery

Abstract

Myogenic tone (MT) of resistance artery, vasoconstriction in response to increasing luminal pressure (Plum), stabilizes regional blood flow albeit the fluctuation of perfusion pressure. The levels of MT differ between vascular beds. Mechanosensitive depolarization of membrane potential and activation of voltage-gated Ca2+ channels (VOCCs) are cellular mechanisms for MT in smooth muscle cells (SMCs). Large-conductance Ca2+-activated K+ channel (BKCa) in SMCs may antagonize the contractile signals in MT. Using video-analysis of pressurized (60 mmHg) artery, we found that MT in mesenteric artery (MA) is significantly smaller than that of cerebral artery (CA). Iberiotoxin, a selective BKCa inhibitor, augmented the MT of MA by larger extent than CA. Patch clamp analysis showed that not only the BKCa current density but also unitary slope conductance of MASMC are higher than CASMCs. In addition, the frequency of spontaneous transient outward currents (STOCs) reflecting the BKCa activity in responses to Ca2+ sparks was higher in MASMCs. Voltage-gated K+ channel (Kv) activity was also higher in MASMCs. Although Ba2+-sensitive inwardly rectifying K+ current is larger in CASMCs, pretreatment with Ba2+did not induce significant augmentation of iberiotoxin sensitivity of MT in CA. Taken together, it is suggested that more frequent STOCs and larger average outward current via BKCa could explain the weak MT in MA.