Effects of oxidants on membrane potential, K+ and Ca2+ currents of mouse pancreatic B-cells.

Abstract

K+ATP channels play a key role in controlling membrane potential and insulin secretion in pancreatic B-cells (Ashcroft and Rorsman, 1989). Therefore, the regulation of these and of other channels involved in the control of the B-cell membrane potential is of great interest. Agents oxidizing SH-groups have been shown to influence K+ channel activity and function in a variety of different cell types such as skeletal muscle cells (Weik and Neumcke, 1989), neurons (Ruppersberg et al., 1991), lung adenocarcinoma cells (Kuo et al., 1993) and liver cells (Hallbrucker et al., 1993). Islam et al. (1993) have shown that the oxidizing agent 2, 2′-dithio-bis(5-nitropyridine) (DTBNP) leads to closure of K+ATP channels in pancreatic B-cells. They propose that this effect would increase insulin secretion. However, it has also been shown that SH-group oxidizing agents diminish insulin release (Ammon et al., 1983), an effect which may be a result of the opening of K+ channels. Our data demonstrate that H2O2 in contrast to DTBNP stimulates the K+ATP current in mouse pancreatic B-cells and that thiol reagents also affect the current through voltage-dependent Ca2+ channels.