Effect of end-stage renal disease on responsiveness to calmodulin and thyroid hormone of calcium-ATPase in human red blood cells.

Red blood cell membrane Ca2+-ATPase, a calcium-pump-associated enzyme, has been studied in a series of 10 patients with ESRD and in a group of normal volunteers. Basal enzyme activity was significantly reduced in cells from ESRD patients (0.189 +/- 0.018 vs. controls, 0.274 +/- 0.021 mumoles of Pi per milligram of membrane protein per 90 min; P less than 0.001). Calcium efflux from intact red cells, a functional correlate of Ca2+-ATPase activity, was also decreased in ESRD patients. Normal erythrocytes have recently been shown to have membrane Ca2+-ATPase activity that can be stimulated in vitro by physiologic concentrations of thyroid hormone (10(-10) M). In the present studies, ESRD red cell membrane Ca2+-ATPase activity was found to be unresponsive to thyroid hormone. In addition, calcium efflux from intact ESRD cells, in contrast to normal red cells, could not be stimulated by thyroid hormone. ESRD membrane Ca2+-ATPase was also poorly-responsive in vitro to purified calmodulin, the activator protein of the enzyme. This reduction in activity of Ca2+-ATPase in ESRD red cells is similar to previously described alterations in sodium-potassium-ATPase, another membrane-linked cation pump.