RECIPROCAL REGULATION OF CARDIAC NA-K-ATPASE AND NA CA EXCHANGER - HYPERTENSION, THYROID-HORMONE, DEVELOPMENT/

Inhibiting cardiac Na pump activity decreases the driving force for th e Na/Ca exchanger transport that increases cellular Ca stores and cont ractility. Decreased abundance of Na pumps would be expected to have t he same effect as decreased activity unless there was reciprocal regul ation of Na/Ca exchanger expression to oppose the effects of depressed Na pump activity on intracellular Ca stores. The aim of this study wa s to test the hypothesis that cardiac Na/Ca exchanger abundance is reg ulated in a reciprocal fashion to Na-K-ATPase abundance in a number of models known to have altered Na-K-ATPase abundance. In renovascular h ypertension, cardiac ventricular Na-K-ATPase alpha(1)-levels are unalt ered, alpha(2)-isoform subunit mRNA and protein levels decrease to 0.7 6 +/- 0.06 and 0.56 +/- 0.07 of control, respectively, and the Na/Ca e xchanger protein (not mRNA) increased 1.35 +/- 0.11-fold. In the trans ition from hypothyroid to hyperthyroid, cardiac alpha(1) doubles, alph a(2)-protein increases 8.83 +/- 1.06-fold, and the Na/Ca exchanger pro tein decreases to 0.64 +/- 0.11. A similar pattern was seen during car diac development in the preweaning rat heart. Treatment with the antia rrhythymic amiodarone has no effect on alpha(1), decreases alpha(2)-pr otein expression to 0.51 +/- 0.08 of control, and increases exchanger expression 1.42 +/- 0.16-fold. In conclusion, the reciprocal regulatio n of the Na/Ca exchanger and of Na-K-ATPase alpha(2)-expression provid es evidence for a homeostatic mechanism that would oppose the changes in cellular Ca stores driven by the changes in Na-K-ATPase activity.