Proton modulation of cardiac I Na: a potential arrhythmogenic trigger.
Handb Exp Pharmacol
; 221: 169-81, 2014.
Article
em En
| MEDLINE
| ID: mdl-24737236
ABSTRACT
Voltage-gated sodium (NaV) channels generate the upstroke and mediate duration of the ventricular action potential, thus they play a critical role in mediating cardiac excitability. Cardiac ischemia triggers extracellular pH to drop as low as pH 6.0, within just 10 min of its onset. Heightened proton concentrations reduce sodium conductance and alter the gating parameters of the cardiac-specific voltage-gated sodium channel, NaV1.5. Most notably, acidosis destabilizes fast inactivation, which plays a critical role in regulating action potential duration. The changes in NaV1.5 channel gating contribute to cardiac dysfunction during ischemia that can cause syncope, cardiac arrhythmia, and even sudden cardiac death. Understanding NaV channel modulation by protons is paramount to treatment and prevention of the deleterious effects of cardiac ischemia and other triggers of cardiac acidosis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Arritmias Cardíacas
/
Sódio
/
Ativação do Canal Iônico
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Miócitos Cardíacos
/
Canal de Sódio Disparado por Voltagem NAV1.5
/
Frequência Cardíaca
Tipo de estudo:
Etiology_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Handb Exp Pharmacol
Ano de publicação:
2014
Tipo de documento:
Article