Phosphocreatine as a determinant of KATP channel activity in pancreatic β-cells
Phosphocreatine as a determinant of KATP channel activity in pancreatic β-cells
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DOI：
10.1007/s00424-002-0975-x
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发表时间：
2003-02-01
影响因子：
4.5
通讯作者：
Drews, G
中科院分区：
文献类型：
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作者：
Krippeit-Drews, P;Bäcker, M;Drews, G
本研究的目的是验证一种假说，即肌酸激酶/磷酸肌酸系统参与调节胰岛β细胞中的K(ATP)通道。当葡萄糖浓度从0.5 mM增加到15 mM时，小鼠胰岛中的磷酸肌酸浓度与ATP/ADP比值明显平行增加。注射磷酸肌酸或三磷酸腺苷可抑制非洲爪哇卵母细胞表达的KATP通道电流，但不能被单独注射磷酸或肌酸所抑制。在从天然β细胞获得的由内向外的P细胞膜上，磷酸肌酸在ADP存在的情况下降低了单个KATP通道的开放概率，但在没有核苷酸的情况下没有降低。这些实验表明，存在一种KATP通道相关的肌酸激酶，它可以磷酸化ADP。肌酸激酶抑制剂碘乙酰胺抑制葡萄糖引起的胞浆Ca(2+)浓度[Ca(2+)]的振荡，提示磷酸肌酸作为能量丰富的磷酸盐从线粒体到质膜的穿梭。这些数据为胰岛β细胞中KATP通道的信号转导提供了一个新的模型。
The aim of the present study was to test the hypothesis that a creatine kinase/phosphocreatine system is involved in the regulation of K(ATP) channels in pancreatic beta-cells. The phosphocreatine concentration in isolated mouse islets clearly increased in parallel with the ATP/ADP ratio in response to a rise of the glucose concentration from 0.5 mM to 15 mM. The currents through KATP channels expressed in oocytes of Xenopus laevis were inhibited by injection of phosphocreatine or ATP but not by phosphate or creatine alone. In inside-out patches of P-cell membranes obtained from native beta-cells, phosphocreatine reduced the open probability of single KATP channels in the presence of ADP but not in the absence of the nucleotide. These experiments suggest the existence of a KATP channel-associated creatine kinase that phosphorylates ADP. The creatine kinase inhibitor iodoacetamide suppressed the glucose-induced oscillations of the cytoplasmic Ca(2+) concentration, [Ca(2+)], It is concluded that phosphocreatine serves as a shuttle for energy-rich phosphate from the mitochondria to the plasma membrane. The data provide a novel model for signal transduction to KATP channels in pancreatic beta-cells.