Pertussis toxin-sensitive pathway inhibits glucose-stimulated Ca2+ signals of rat islet β-cells by affecting L-type Ca2+ channels and voltage-dependent K+ channels

Abstract A role of pertussis toxin (PTX)-sensitive pathway in regulation of glucose-stimulated Ca 2+ signaling in rat islet β-cells was investigated by using clonidine as a selective agonist to α 2 -adrenoceptors which link to the pathway. An elevation of extracellular glucose concentration from 5.5 to 22.2 mM (glucose stimulation) increased the levels of [Ca 2+ ] i of β-cells, and clonidine reversibly reduced the elevated levels of [Ca 2+ ] i . This clonidine effect was antagonized by yohimbine, and abolished in β-cells pre-treated with PTX. Clonidine showed little effect on membrane currents including those through ATP-sensitive K + channels induced by voltage ramps from −90 to −50 mV. Clonidine showed little effect on the magnitude of whole-cell currents through L-type Ca 2+ channels ( I Ca(L) ), but increased the inactivation process of the currents. Clonidine increased the magnitude of the voltage-dependent K + currents ( I VK ). These clonidine effects on I Ca(L) and I VK were abolished in β-cells treated with PTX or GDP-βS. These results suggest that the PTX-sensitive pathway increases I VK activity and decreases I Ca(L) activity of islet β-cells, resulting in a decrease in the levels of [Ca 2+ ] i elevated by depolarization-induced Ca 2+ entry. This mechanism seems responsible at least in part for well-known inhibitory action of PTX-sensitive pathway on glucose-stimulated insulin secretion from islet β-cells.