REGULATION OF ATP-SENSITIVE K+ CHANNELS BY ATP AND NUCLEOTIDE DIPHOSPHATE IN RABBIT PORTAL-VEIN

The modulation of ATP-sensitive K+ (K-ATP)-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 K-ATP channels in the cell-attached configuration. After patch excision, K-ATP channels showed ''run-down'' phenomenon in the presence of KCOs, but subsequent application of Mg-ATP (1 mM) restored K-ATP-channel activity. Removal of Mg-ATP resulted in transient augmentation of K-ATP 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 K-ATP-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 K-ATP channels (operative and inoperative states) and that KCOs open K-ATP channels only in the operative state.