Calcium adaptation to sodium pump inhibition in a human megakaryocytic cell line.
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 alpha1- and alpha3-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.
Kimura
Masayuki
M
Hypertension Research Center, Rm. F-464, MSB, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 South Orange Ave., Newark, New Jersey 07103, USA.
Cao
Xiaojian
X
Aviv
Abraham
A
D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008533:Megakaryocytes / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D021122:Protein Subunits; D012519:Sarcoplasmic Reticulum / Q000502:physiology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D012964:Sodium / Q000502:physiology; D019831:Sodium-Calcium Exchanger / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D007527:Isoenzymes; D021122:Protein Subunits; D019831:Sodium-Calcium Exchanger; D010042:Ouabain; D012964:Sodium; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium