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L‐type calcium channel as a cardiac oxygen sensor
Author(s) -
Movafagh Shahrzad,
Morad Martin
Publication year - 2010
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2009.05095.x
Subject(s) - thapsigargin , phosphorylation , chemistry , biophysics , calcium , protein subunit , l type calcium channel , voltage dependent calcium channel , biochemistry , microbiology and biotechnology , biology , intracellular , organic chemistry , gene
Acute oxygen sensing in the heart is thought to occur through redox regulation and phosphorylation of membrane channels. Here we report a novel O 2 ‐sensing mechanism involving the C‐terminus of the L‐type Ca 2+ channel and regulated by PKA phosphorylation. In patch‐clamped myocytes, oxygen deprivation decreased I Ca within 40 s. The suppressive effect of anoxia was relieved by PKA‐mediated phosphorylation only when Ca 2+ was the charge carrier, whereas phosphorylated I Ba remained sensitive to O 2 withdrawal. Suppression of Ca 2+ release by thapsigargin did not alter the response of I Ca to anoxia, suggesting a mandatory role for Ca 2+ influx and not Ca 2+ ‐induced Ca 2+ release (CICR) in O 2 regulation of the channel. Consistent with this idea, mutation of 80 amino acids in the Ca 2+ /CaM‐binding domain of the recombinant α 1C subunit that removes Ca 2+ dependent inactivation (CDI) abolished O 2 sensitivity of the channel. Our findings suggest that the Ca 2+ /CaM binding domain of the L‐type Ca 2+ may represent a molecular site for O 2 sensing of the heart.