Open AccessCalmodulin kinase is a molecular switch for cardiac excitation –contraction coupling
Author(s) -
Yuejin Wu,
Roger J. Colbran,
Mark E. Anderson
Publication year - 2001
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.051449198
Subject(s) - ryanodine receptor , camk , calmodulin , endoplasmic reticulum , biophysics , intracellular , cardiac muscle , myocyte , microbiology and biotechnology , chemistry , skeletal muscle , protein kinase a , kinase , calcium , biology , endocrinology , autophosphorylation , organic chemistry
Signaling between cell membrane-bound L-type Ca(2+) channels (LTCC) and ryanodine receptor Ca(2+) release channels (RyR) on sarcoplasmic reticulum (SR) stores grades excitation-contraction coupling (ECC) in striated muscle. A physical connection regulates LTCC and RyR in skeletal muscle, but the molecular mechanism for coordinating LTCC and RyR in cardiomyocytes, where this physical link is absent, is unknown. Calmodulin kinase (CaMK) has characteristics suitable for an ECC coordinating molecule: it is activated by Ca(2+)/calmodulin, it regulates LTCC and RyR, and it is enriched in the vicinity of LTCC and RyR. Intact cardiomyocytes were studied under conditions where CaMK activity could be controlled independently of intracellular Ca(2+) by using an engineered Ca(2+)-independent form of CaMK and a highly specific CaMK inhibitory peptide. CaMK reciprocally enhanced L-type Ca(2+) current and reduced release of Ca(2+) from the SR while increasing SR Ca(2+) content. These findings support the hypothesis that CaMK is required to functionally couple LTCC and RyR during cardiac ECC.