Submitted on February 24, 2005
Accepted on May 25, 2005
Calcium Adaptation to Na-pump Inhibition in a Human Megakaryocytic Cell Line
Masayuki Kimura1, Xiaojian Cao1, and Abraham Aviv1*
1 Hypertension Research Center, University of Medicine & Dentistry of NJ, Newark, New Jersey, USA
* To whom correspondence should be addressed. E-mail: avivab{at}umdnj.edu.
The unique characteristics of the platelet Na/Ca exchanger, i.e., its dependency on both the trans-membrane 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 
1 and 3 isoforms of the Na-K-ATPase. Inhibition of the Na-pump increased the RNA and protein expressions of the sarco(endo)plasmic reticulum (SERCA) 2b, cytosolic Na and Ca and the freely exchangeable calcium 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 to platelet biology are discussed.
