title: Vanadate as an activator of ATP--sensitive potassium channels in mouse skeletal muscle.
abstract: The inside-out mode of the patch-clamp technique was used to study adenosine-5'-triphosphate (ATP)-sensitive K+ channels in mammalian skeletal muscle. Vanadate, applied to the cytoplasmic face of excised patches, was a potent activator of ATP-sensitive K+ channels. Divalent cations (Mg2+, Ca2+) were a prerequisite for the activating process. The maximal effect was achieved using 1 mM vanadate dissolved in Ringer, increasing the open-state probability about ninefold. The active 5 + redox form of vanadate which stimulates ATP-sensitive K+ channels is likely to be decavanadate V10O28(6-). ATP concentration-response curves have Hill coefficients near three internal Na(+)-rich Ringer and between one and two in internal KCl solutions. Half-maximal channel blockage was observed at ATP concentrations of 4 and 8 microM in Ringer and KCl solutions, respectively. Internal vanadate shifted the curves towards higher ATP concentrations without affecting their slopes. Thus 50% channel blockage occurred at 65 microM ATP in internal Ringer containing 0.5 mM vanadate. The results indicate that the affinity and stoichiometry of ATP binding to ATP-sensitive K+ channels are strongly modulated by internal cations and that the ATP sensitivity is weakened by vanadate.
authors.affiliation: I. Physiologisches Institut, Universität des Saarlandes, Homburg/Saar, Federal Republic of Germany.
authors.forename: B
authors.initials: B
authors.lastname: Neumcke
authors.forename: R
authors.initials: R
authors.lastname: Weik
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D007424:Intracellular Fluid / Q000737:chemistry; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials; D051379:Mice; D009132:Muscles / Q000166:cytology / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology*
chemical_list: D015221:Potassium Channels; D014638:Vanadates; D000255:Adenosine Triphosphate