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Mol Pharmacol. 2009 Apr;75(4):774-81. doi: 10.1124/mol.108.052597. Epub 2009 Jan 2.

Activation of (Na+ + K+)-ATPase modulates cardiac L-type Ca2+ channel function.

Author information

1
Department of Biochemistry, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Abstract

Cellular Ca(2+) signaling underlies diverse vital biological processes, including muscle contractility, memory encoding, fertilization, cell survival, and cell death. Despite extensive studies, the fundamental control mechanisms that regulate intracellular Ca(2+) movement remain enigmatic. We have found recently that activation of the (Na(+)+K(+))-ATPase markedly potentiates intracellular Ca(2+) transients and contractility of rat heart cells. Little is known about the pathway responsible for the activation of the (Na(+)+K(+))-ATPase-initiated Ca(2+) signaling. Here, we demonstrate a novel mechanism in which activation of the (Na(+)+K(+))-ATPase is coupled to increased L-type Ca(2+) channel function through a signaling cascade involving Src and ERK1/2 but not well established regulators of the channel, such as adrenergic receptor system or activation of PKA or CaMKII. We have also identified Ser(1928), a phosphorylation site for the alpha1 subunit of the L-type Ca(2+) channel that may participate in the activation of the (Na(+)+K(+))-ATPase-mediated Ca(2+) signaling. The findings reported here uncover a novel molecular cross-talk between activation of the (Na(+)+K(+))-ATPase and L-type Ca(2+) channel and provide new insights into Ca(2+) signaling mechanisms for deeper understanding of the nature of cellular Ca(2+) handling in heart.

PMID:
19122004
PMCID:
PMC2658729
DOI:
10.1124/mol.108.052597
[Indexed for MEDLINE]
Free PMC Article

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