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Am J Physiol Cell Physiol 289: C891-C897, 2005. First published June 1, 2005; doi:10.1152/ajpcell.00080.2005
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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Calcium adaptation to sodium pump inhibition in a human megakaryocytic cell line

Masayuki Kimura, Xiaojian Cao, and Abraham Aviv

Hypertension Research Center, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey

Submitted 24 February 2005 ; accepted in final form 25 May 2005

The unique characteristics of the platelet Na/Ca exchanger, i.e., its dependence on both transmembrane Na and K gradients, render it highly sensitive to Na pump inhibition. In this project, we observed that the human megakaryocytic cell line CHRF-288 expresses both the {alpha}1- and {alpha}3-isoforms of the Na-K-ATPase. Inhibition of the Na pump increased the RNA and protein expressions of sarco(endo)plasmic reticulum Ca-ATPase 2b, cytosolic Na and Ca, and the freely exchangeable Ca in the endoplasmic reticulum. These changes occurred in concert with diminished store-operated Ca entry and an increase in the maximal activity of the Na/Ca exchanger. Inhibition of the Na pump by ouabain was more effective in inducing these changes than diminishing medium K. Collectively, these observations point to an integrative effort to counteract the impact of Na pump inhibition by Ca sequestration into the endoplasmic reticulum, diminished Ca entry, and increased activity of the Na/Ca exchanger. The implications of these findings in platelet biology are discussed.

platelets; thrombosis; potassium; stroke


Address for reprint requests and other correspondence: A. Aviv, Hypertension Research Ctr., Rm. F-464, MSB, Univ. of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 South Orange Ave., Newark, NJ 07103 (e-mail: avivab{at}umdnj.edu)






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