Rapid Na+ accumulation by a sustained action potential impairs mitochondria function and induces apoptosis in HEK293â¯cells expressing non-inactivating Na+ channels.
Biochem Biophys Res Commun
; 513(1): 269-274, 2019 05 21.
Article
em En
| MEDLINE
| ID: mdl-30952429
ABSTRACT
The mechanisms underlying neuronal cell death induced by the rise of intracellular Na+ concentration ([Na+]i) following abnormal hyperexcitation are not fully understood. Previously, we have established a recombinant cell line derived from HEK293â¯cells, in which the occurrence of a sustained action potential (AP) induces cell death. Mutated voltage-gated Nav1.5 channel (IFM/QQQ) lacking inactivation, and inward rectifying K+ channel (Kir2.1) were co-expressed in HEK293 cells (IFM/QQQ + Kir2.1 cells). In this cell line, the rise of [Na+]i due to a sustained AP reached maximum within 15â¯min without concomitant [Ca2+]i rise, and then elicited significant externalization of phosphatidylserine and enhancement of caspase activity. Marked decreases in mitochondrial transmembrane potential and ATP concentration were also detected. The significant cell death occurred at 3â¯h from the AP onset and reached a steady state at around 12â¯h. The significant release of lactate dehydrogenase was not detected even after 12â¯h. These results provide novel findings that Na+ accumulation or/and possibly concomitant K+ loss elicits apoptosis presumably due to the mitochondrial dysfunction, which is attributable to neither the membrane depolarization nor [Ca2+]i change. This apoptotic mechanism may be involved, at least in part, in neuronal cell death under pathophysiological settings with abnormal hyperexcitability.
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Base de dados:
MEDLINE
Assunto principal:
Sódio
/
Potenciais de Ação
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Apoptose
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Células Epiteliais
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Canal de Sódio Disparado por Voltagem NAV1.5
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article