Pressure-induced oxidative activation of PKG enables vasoregulation by Ca2+ sparks and BK channels.

ABSTRACT: Activation of Ca²⁺-sensitive, large-conductance potassium (BK) channels in vascular smooth muscle cells (VSMCs) by local, ryanodine receptor-mediated Ca²⁺ signals (Ca²⁺ sparks) acts as a brake on pressure-induced (myogenic) vasoconstriction-a fundamental mechanism that regulates blood flow in small resistance arteries. We report that physiological intraluminal pressure within resistance arteries activated cGMP-dependent protein kinase (PKG) in VSMCs through oxidant-induced formation of an intermolecular disulfide bond between cysteine residues. Oxidant-activated PKG was required to trigger Ca²⁺ sparks, BK channel activity, and vasodilation in response to pressure. VSMCs from arteries from mice expressing a form of PKG that could not be activated

SUBMITTER: Khavandi K 

PROVIDER: S-EPMC5154376 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature