Pressure-induced oxidative activation of PKG enables vasoregulation by Ca2+ sparks and BK channels.
Sci Signal
; 9(449): ra100, 2016 10 11.
Article
em En
| MEDLINE
| ID: mdl-27729550
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 by oxidants showed reduced Ca2+ 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 Ca2+ sparks.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vasoconstrição
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Pressão Sanguínea
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Proteínas Quinases Dependentes de GMP Cíclico
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Sinalização do Cálcio
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Miócitos de Músculo Liso
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Mecanotransdução Celular
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Canais de Potássio Ativados por Cálcio de Condutância Alta
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Músculo Liso Vascular
Limite:
Animals
Idioma:
En
Revista:
Sci Signal
Ano de publicação:
2016
Tipo de documento:
Article