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.
|Journal||American Journal of Physiology - Heart and Circulatory Physiology|
|Issue number||5 35-5|
|Publication status||Published - 1994|
All Science Journal Classification (ASJC) codes
- Cardiology and Cardiovascular Medicine
- Physiology (medical)