Altered cytosolic calcium homeostasis in rat cardiac myocytes in CRF

Abstract

Chronic renal failure (CRF) is associated with an increase in calcium content of heart. This was attributed to the secondary hyperparathyroidism of CRF, since PTH augments entry of calcium into cardiac myocytes. At present, it is not known whether the increase in calcium content of heart reflects a rise in basal levels of cytosolic calcium ([Ca2+]) of cardiac myocytes. Further, in order for the PTH-induced entry of calcium into cardiac myocytes to raise their basal levels of [Ca2+](i), calcium extrusion out of these cells should be impaired as well. The present study examined the effect of CRF with and without excess PTH (PTX) and of the treatment of CRF rats with verapamil on basal levels of [Ca2+](i) and ATP content of cardiac myocytes and on the activities of the pumps that are directly (Ca2+-ATPase and Na+- Ca2+ exchanger) and indirectly (Na+-K+ ATPase) responsible for calcium extrusion out of these cells. The basal levels of [Ca2+](i) of cardiac myocytes increased (P < 0.01) and their ATP content decreased (P < 0.01) as the duration of CRF advanced. CRF was associated with significant decrement in V(max) of Ca2+ ATPase and Na+-K+ATPase and in Na+-Ca2+ exchange. These derangements were prevented by prior PTX of the CRF rats or by their treatment with verapamil. The data indicate that (1) CRF is associated with a significant rise in basal levels of [Ca2+](i) of cardiac myocytes, (2) this effect is mediated by the state of secondary hyperparathyroidism of CRF, and (3) the pathways through which excess PTH in CRF generates this effect include both increased entry of calcium into cardiac myocytes and decreased exit of this ion out of these cells.