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Role of T‐type Ca2+ channel in hypernatremic precondition
Author(s) -
Pastukh Viktor,
Ricci Craig,
Wu Songwei,
Gillespie Mark N.,
Schaffer Stephen W.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.751.16
Subject(s) - hypernatremia , downregulation and upregulation , hypoxia (environmental) , sodium , extracellular , medicine , chemistry , endocrinology , biochemistry , organic chemistry , oxygen , gene
Hypernatremia is a well established risk factor for heart disease. However, the actions of salt excess are complex and their interactions with ischemic injury remain unclear. The present study examined whether chronic extracellular sodium treatment could precondition the cardiomyocyte against hypoxia‐mediated cell death. Cardiomyocytes were incubated during the pre‐hypoxic period with medium containing either 167 mM Na + (hypernatremia), 50 mM Mannitol (hyperosmotic) or 142 mM Na + (control). Hypernatremia rendered the cells resistant to hypoxia‐mediated cell death, an effect linked to a significant reduction in Ca 2+ accumulation. The reduction in [Ca 2+ ] I was associated with decreased T‐type Ca 2+ current but not L‐type Ca 2+ current. This effect appeared to be specific for hypernatremia, as there was no change in the T‐type Ca 2+ channel in the hyperosmotically treated cells. Downregulation of the Ca v 3.1 variant of the T‐type Ca 2+ channel using iRNA also led to a reduction in hypoxia‐mediated Ca 2+ accumulation and cell death. Therefore, downregulation of the Ca v 3.1 variant is cytoprotective and contributes to the development of hypernatremic preconditioning.