NISOLDIPINE BLOCKS THE INCREASE OF INTRACELLULAR FREE CALCIUM-ION CONCENTRATION ASSOCIATED WITH ELEVATED SODIUM-LITHIUM COUNTERTRANSPORT ACTIVITY IN ERYTHROCYTES IN PATIENTS WITH NIDDM

To understand the mechanism by which elevated sodium-lithium countertr ansport activity (SLC) associates with increased intracellular free ca lcium-ion concentration ([Ca2+](i)), we investigated the relationship between SLC and the effects of the extracellular Ca2+ concentration ([ Ca2+](o)) and a Ca2+-channel blocker, nisoldipine, on [Ca2+](i) in ery throcytes from 48 patients with non-insulin-dependent (Type 2) diabete s mellitus (NIDDM). There was a significant correlation between SLC an d [Ca2+](i). Nisoldipine in the incubation medium significantly decrea sed [Ca2+](i), and there was a significant positive correlation betwee n SLC and the degree of [Ca2+](i) decrease. When the [Ca2+](o) was ele vated, [Ca2+](i) was significantly increased, but nisoldipine almost c ompletely suppressed this increase of [Ca2+](i). There was a significa nt positive correlation between SLC and the degree of the suppression. These data suggest that elevated SLC correlates with increased [Ca2+] (i), and that the increased [Ca2+](i) might be due to the increased Ca 2+ influx through a dihydropyridine-sensitive Ca2+ pathway. (C) 1997 b y John Wiley & Sons, Ltd.