Contribution of Na+/Ca2+ exchanger to glucose-induced [Ca2+]i increase in rat pancreatic islets

The present study was carried out to elucidate the role of the reverse mode of the Na+/Ca2+ exchanger in an increase in intracellular Ca2+ concentration ([Ca2+](i)) induced by a stimulatory concentration of glucose in rat pancreatic islets. The effects of KB-R7943, a selective inhibitor of reverse Na+/Ca2+ exchanger, on Na-o(+) removal-induced [Ca2+](i) changes were examined by a microfluorimetric method using fura-2 in perifused preparations of isolated rat pancreatic islets. Na-o(+) removal induced a rapid increase in [Ca2+](i) under 100 or 5 mM K+ conditions, respectively. The increases in [Ca2+](i) induced by Na-o(+) removal were inhibited by KB-R7943. The net amount of the [Ca2+](i) increases during Na-o(+) removal (Delta[Ca2+](i)), obtained by subtracting the KB-R7943-independent Delta[Ca2+](i) in the presence of KB-R7943 from Delta[Ca2+](i) in the absence of KB-R7943, was significantly increased when extracellular K+ was raised. Increasing the external glucose concentration from 3 to 20 mM caused a biphasic increase in [Ca2+](i), which exhibited a transient increase (first phase) followed by a sustained increase (second phase) in [Ca2+](i). KBR7943 (10 mu M) partially inhibited the second phase of the [Ca2+](i) increase rather than the first phase. These results suggest that the increase in [Ca2+](i) induced by Na-o(+) removal may be enhanced when plasma membrane is depolarized, and consequently Ca2+ influx through the reverse Na+/Ca2+ exchanger may partially contribute to the glucose-induced [Ca2+](i) dynamics in rat pancreatic islet cells.