Activation of (Na+ + K+)-ATPase modulates cardiac L-type Ca2+ channel function.
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.
Lee
Dong I
DI
Department of Biochemistry, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Klein
Michael G
MG
Zhu
Weizhong
W
Xiao
Rui-Ping
RP
Gerzanich
Volodymyr
V
Xu
Kai Y
KY
D000595:Amino Acid Sequence; D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D008297:Male; D008969:Molecular Sequence Data; D032383:Myocytes, Cardiac / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism* / Q000502:physiology
D020746:Calcium Channels, L-Type; D000254:Sodium-Potassium-Exchanging ATPase