Abstract
Iptakalim hydrochloride (IPT) is a novel ATP-sensitive potassium channel (K(ATP)) opener which has a different chemical structure from any other known K(ATP) opener, and produces vasodilution. In this study, we examined the effect of IPT on rat pancreatic beta-cell functions. In the perifusion experiment for islets, an application of IPT increased insulin secretion, tested with 5.5 mM glucose in the extracellular solution. Examined in isolated beta-cells loaded with fura-2, IPT elevated intracellular calcium concentration, which was restored by diazoxide. Under the patch-clamp whole-cell configuration, IPT induced depolarization in isolated beta-cells followed by action potential firing. The depolarization was associated with a decrease in membrane conductance resulting from a decrease in K(ATP) activity. Further, IPT applied into the bath solution inhibited K(ATP), recorded in the cell-attached mode. IPT applied to the intracellular surface of the membrane also inhibited K(ATP), recorded in the inside-out mode. These results indicate that IPT acts on pancreatic beta-cells as a K(ATP) blocker, which in turn causes electrical excitation of the cell and insulin secretion. [J Physiol Sci. 2006;56 Suppl:S114]
