Hypoxia Produces Pro-arrhythmic Late Sodium Current in Cardiac Myocytes by SUMOylation of NaV1.5 Channels.
Cell Rep
; 30(7): 2225-2236.e4, 2020 02 18.
Article
em En
| MEDLINE
| ID: mdl-32075761
ABSTRACT
Acute cardiac hypoxia produces life-threatening elevations in late sodium current (ILATE) in the human heart. Here, we show the underlying mechanism hypoxia induces rapid SUMOylation of NaV1.5 channels so they reopen when normally inactive, late in the action potential. NaV1.5 is SUMOylated only on lysine 442, and the mutation of that residue, or application of a deSUMOylating enzyme, prevents hypoxic reopenings. The time course of SUMOylation of single channels in response to hypoxia coincides with the increase in ILATE, a reaction that is complete in under 100 s. In human cardiac myocytes derived from pluripotent stem cells, hypoxia-induced ILATE is confirmed to be SUMO-dependent and to produce action potential prolongation, the pro-arrhythmic change observed in patients.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sódio
/
Hipóxia Celular
/
Miócitos Cardíacos
/
Sumoilação
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Canal de Sódio Disparado por Voltagem NAV1.5
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article