Details

Autor(en) / Beteiligte

• Khavandi, Kaivan
• Baylie, Rachael A
• Sugden, Sarah A
• Ahmed, Majid
• Csato, Viktoria
• Eaton, Philip
• Hill-Eubanks, David C
• Bonev, Adrian D
• Nelson, Mark T
• Greenstein, Adam S

Titel

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

Ist Teil von

• Science signaling, 2016-10, Vol.9 (449), p.ra100

Ort / Verlag

United States

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• Activation of Ca -sensitive, large-conductance potassium (BK) channels in vascular smooth muscle cells (VSMCs) by local, ryanodine receptor-mediated Ca signals (Ca 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 Ca 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 by oxidants showed reduced Ca spark frequency, and arterial preparations from these mice had decreased pressure-induced activation of BK channels. Thus, the absence of oxidative activation of PKG disabled the BK channel-mediated negative feedback regulation of vasoconstriction. Our results support the concept of a negative feedback control mechanism that regulates arterial diameter through mechanosensitive production of oxidants to activate PKG and enhance Ca sparks.