Kamouchi M, Kitamura K
Department of Pharmacology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Am J Physiol. 1994 May;266(5 Pt 2):H1687-98. doi: 10.1152/ajpheart.1994.266.5.H1687.
The modulation of ATP-sensitive K+ (KATP)-channel activity was investigated by recording single-channel currents in isolated smooth muscle cells from rabbit portal vein. K(+)-channel openers (KCOs; pinacidil, lemakalim, and nicorandil) induced burstlike openings of single KATP channels in the cell-attached configuration. After patch excision, KATP channels showed "run-down" phenomenon in the presence of KCOs, but subsequent application of Mg-ATP (1 mM) restored KATP-channel activity. Removal of Mg-ATP resulted in transient augmentation of KATP currents, which eventually decayed out. Nucleotide diphosphates (NDPs; GDP, ADP, UDP, IDP, and CDP) also induced channel reopening in the presence of KCOs, which was markedly enhanced by addition of Mg2+ in millimolar concentrations at the internal side of the membrane. The dose-response relation between ATP and the UDP-induced KATP-channel activity was shifted to the right in the presence of Mg2+ (2 mM). These results suggest that intracellular ATP, NDPs, and Mg2+ regulate the channel state of KATP channels (operative and inoperative states) and that KCOs open KATP channels only in the operative state.
通过记录兔门静脉分离平滑肌细胞中的单通道电流，研究了ATP敏感性钾（KATP）通道活性的调节。钾通道开放剂（KCOs；匹那地尔、雷马卡林和尼可地尔）在细胞贴附模式下诱导单个KATP通道出现爆发样开放。膜片钳切除后，在存在KCOs的情况下，KATP通道出现“ rundown”现象，但随后施加Mg-ATP（1 mM）可恢复KATP通道活性。去除Mg-ATP导致KATP电流短暂增强，最终衰减消失。核苷酸二磷酸（NDPs；GDP、ADP、UDP、IDP和CDP）在存在KCOs的情况下也诱导通道重新开放，在膜内侧加入毫摩尔浓度的Mg2+可显著增强这种开放。在存在Mg2+（2 mM）的情况下，ATP与UDP诱导的KATP通道活性之间的剂量反应关系向右移动。这些结果表明，细胞内ATP、NDPs和Mg2+调节KATP通道的通道状态（开放和关闭状态），并且KCOs仅在开放状态下打开KATP通道。
