RT Journal Article
SR Electronic
T1 Activation of (Na<sup>+</sup>+K<sup>+</sup>)-ATPase Modulates Cardiac L-Type Ca<sup>2+</sup> Channel Function
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 774
OP 781
DO 10.1124/mol.108.052597
VO 75
IS 4
A1 Dong I. Lee
A1 Michael G. Klein
A1 Weizhong Zhu
A1 Rui-Ping Xiao
A1 Volodymyr Gerzanich
A1 Kai Y. Xu
YR 2009
UL http://molpharm.aspetjournals.org/content/75/4/774.abstract
AB Cellular Ca2+ 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 Ca2+ movement remain enigmatic. We have found recently that activation of the (Na++K+)-ATPase markedly potentiates intracellular Ca2+ transients and contractility of rat heart cells. Little is known about the pathway responsible for the activation of the (Na++K+)-ATPase-initiated Ca2+ signaling. Here, we demonstrate a novel mechanism in which activation of the (Na++K+)-ATPase is coupled to increased L-type Ca2+ 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 Ser1928, a phosphorylation site for the α1 subunit of the L-type Ca2+ channel that may participate in the activation of the (Na++K+)-ATPase-mediated Ca2+ signaling. The findings reported here uncover a novel molecular cross-talk between activation of the (Na++K+)-ATPase and L-type Ca2+ channel and provide new insights into Ca2+ signaling mechanisms for deeper understanding of the nature of cellular Ca2+ handling in heart. U.S. Government work not protected by U.S. copyright