Abstract
The K-ATP channel plays a mojor role in coupling the metabolic state to the electrical activity of plasma membranes in several cells. Endosulfine was identified as the endogenious regulator of K-ATP channels. Endosulfine belongs to a highly conserved family of aAMP-regulated phosphoprotein (ARPP) that includes ARPP-16, ARPP-19, ARPP-21 and DARPP-32. The biological function of endosulfine/ARPP has not been understood. In this study, we examined the mechanisms of effects of endosulfine/ARPP on K-ATP channels. Inside-out patchclamp analysis showed that exogenously addministered endosulfine inhibited the current of K-ATP channels of pancreatic beta-cells, while ARPP had no effect. The cell-attached patchclamp analysis showed that the beta-cell transfected with adenovirus expressing endosulfine exhibited action potentials at low glucose states. This result indicates that not only ARPP but also endosulfine reacts with the K-ATP channel as an intracellular ligand to inhibit its channel activity. However, endogenous endosulfine is expressed in pancreatic delta-cells but not beta-cells. Since the threshold glucose concentration for activation of delta-cells is lower than that of beta-cells, the higher sensitivity for glucose in delta-cells may be in part due to the expression of and regulation by endosulfine. [Jpn J Physiol 54 Suppl:S129 (2004)]
