The role of Mg2+ in the inactivation of inwardly rectifying K+ channels in aortic endothelial cells.
We have studied the role of Mg2+ in the inactivation of inwardly rectifying K+ channels in vascular endothelial cells. Inactivation was largely eliminated in Mg(2+)-free external solutions and the extent of inactivation was increased by raising Mg2+o. The dose-response relation for the reduction of channel open probability showed that Mg2+o binds to a site (KD = approximately 25 microM at -160 mV) that senses approximately 38% of the potential drop from the external membrane surface. Analysis of the single-channel kinetics showed that Mg2+ produced a class of long-lived closures that separated bursts of openings. Raising Mg2+o reduced the burst duration, but less than expected for an open-channel blocking mechanism. The effects of Mg2+o are antagonized by K+o in manner which suggests that K+ competes with Mg2+ for the inactivation site. Mg2+o also reduced the amplitude of the single-channel current at millimolar concentrations by a rapid block of the open channel. A mechanism is proposed in which Mg2+ binds to the closed channel during hyperpolarization and prevents it from opening until it is occupied by K+.
Elam
T R
TR
Department of Physiology, University of California School of Medicine, San Francisco 94143-0450, USA.
Lansman
J B
JB
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002417:Cattle; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D008274:Magnesium / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*
D015221:Potassium Channels; D015124:8-Bromo Cyclic Adenosine Monophosphate; D008274:Magnesium