FACTORS OF STRUCTURE AND FUNCTION COUPLING BETWEEN SUR/KIR6.2IN PANCREATIC B-CEELS

ATP-sensitive K1 + K1 channels play an important role in the glucose-stimulated insulin secretion in pancreatic？-cells。该通道确定了恢复膜的潜力，而通道的关闭是在葡萄糖刺激的β-细胞中出现的第一个事件。它已经被证实，硫醚作为胰岛素保密的一个结果，即通过绑定到其受体的K-ATP通道的封闭。该信道由硫醚受体、SUR和不受限制的信道组成， Kir6.2。We studed a mManagement ism underlying signal transduction from the SUR to Kir6. 2 and following results were obtained。（1） Tolbutamde （SU） inhibited the ATP-sensitive KイD1+イエD1 channels。The sensitivity of the channel to tolburtamide was reduced after the treatment of the channel with 2-M Ca-D12+-D1。（2）就在这一次，ADP对渠道活动的影响消失了。（3）ATP通道的敏感性保持正常。（4）PIP 2，Oracle brane phospholipid， prevented the loss of tolbutamide sensitivity induced by CaイイD12+イエD1。（5） From these results， we suggest that CaイイD12+イエD1 may influence the channel protein by decreasing the sensitivity to tolbutamide and ADP。PIP 2 may be reduced by the treatment with high CaイD12+イエD1。这些可能与从SUR到Kir6.2和PIP 2的信号进行交互，我需要在两个子单位之间保持信号。（6）已知与B细胞类型K-ATP通道类似的通道在myocardial细胞中被描述。当PIP 2被披露为提取ATP的细胞时，K-ATP通道当前被降解。

ATP-sensitive KィイD1+ィエD1 channels play an important role in the glucose-stimulated insulin secretion in pancreatic β-cells. The channel determine the resting membrane potential of β-cells and closure of the channel is the first event appeared in glucose-stimulated β-cells. It has been established that sulfonylureas initiate the insulin secretion as a result of closure of the K-ATP channel by binding to their receptor. The channel is composed of sulfonylureas receptor, SUR, and inwardly rectifying channel, Kir6.2. We studied a mechanism underlying signal transduction from the SUR to Kir6.2 and following results were obtained.(1) Tolbutamde (SU) inhibited the ATP-sensitive KィイD1+ィエD1 channels. The sensitivity of the channel to tolburtamide was reduced after the treatment of the channel with 2 μM CaィイD12+ィエD1.(2) At this time, the increasing effect of ADP on the channel activity disappeared.(3) The sensitivity of the channel to ATP was kept normal.(4) PIP2, membrane phospholipid, prevented the loss of tolbutamide sensitivity induced by CaィイD12+ィエD1.(5) From these results, we suggest that CaィイD12+ィエD1 may influence the channel protein by decreasing the sensitivity to tolbutamide and ADP. PIP2 may be reduced by the treatment with high CaィイD12+ィエD1. These may interfarewith the signalling from SUR to Kir6.2 and PIP2 my be required for maintaining the signalling between both subunits.(6) It has been known that the channel similar to b-cell type K-ATP channel is expressed in the myocardial cells. When PIP2 was decerased by exposure of cells to extracellular ATP, the K-ATP channel current was decreased.