Activation of (Na + + K +)-ATPase modulates cardiac L-type Ca 2+ channel function

Dong I. Lee, Michael G. Klein, Weizhong Zhu, Rui Ping Xiao, Volodymyr Gerzanich, Kai Y. Xu

Research output: Contribution to journalArticlepeer-review

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-initi- ated 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 recepto system or activation of PKA or CaMKII. We have also identified Ser 1928, a phosphorylation site for the α1 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.

Original languageEnglish (US)
Pages (from-to)774-781
Number of pages8
JournalMolecular Pharmacology
Volume75
Issue number4
DOIs
StatePublished - Apr 2009
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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