Abstract
A role of pertussis toxin (PTX)-sensitive pathway in regulation of glucose-stimulated Ca2+ signaling in rat islet β-cells was investigated by using clonidine. In isolated β-cells, clonidine reversibly reduced the levels of intracellular Ca2+ concentration ([Ca2+]i) elevated by glucose stimulation (elevation of extracellular glucose concentration from 5.5 to 22.2 mM). This clonidine effect was antagonized by yohimbine, and abolished in β-cells pre-treated with PTX. Clonidine showed little effect on the peak magnitude of whole-cell currents through L-type Ca2+ channels (ICa(L)), but increased the inactivation process of the currents. Clonidine increased the magnitude of the voltage-dependent K+ currents (IVK) in a concentration-dependent manner. These clonidine effects on ICa(L) and IVK were abolished in β-cells treated with PTX. On the other hand, clonidine was ineffective to ATP-sensitive K+ channels. These results suggest that the PTX-sensitive pathway increases IVK activity and decreases ICa(L) activity of islet β-cells, resulting in a decrease in the levels of [Ca2+]i elevated by depolarization-induced Ca2+ 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. [Jpn J Physiol 54 Suppl:S73 (2004)]
