Activation of ATP-dependent K+ channels by metabolic poisoning in adult mouse skeletal muscle: role of intracellular Mg(2+) and pH.
1. The effects of metabolic poisoning, intracellular Mg(2+) and pH on ATP-dependent K+ (K+ATP) channels were examined in adult mouse isolated skeletal muscle fibres using the patch clamp technique. 2. In cell-attached membrane patches, while openings of one kind of channel could only rarely be detected under control conditions, cell poisoning with fluorodinitrobenzene (FDNB), dinitrophenol (DNP) and cyanide (CN) induced a strong and partially reversible increase in channel activity. 3. Slope conductance and glibenclamide sensitivity of this outward current indicated that the channel activated during poisoning was the K+ATP channel. 4. Single channel current amplitude was reduced during poisoning, but remained unchanged when activation of the K+ATP channel was induced by cromakalim. 5. In inside-out membrane patches, in the absence of intracellular ATP, intracellular application of Mg2+ decreased channel activity and single channel current amplitude. Inhibition of K+ATP channels by ATP was also reduced. 6. In the absence of intracellular ATP, a decrease in intracellular pH induced a reduction in channel activity and single channel current amplitude. Inhibition of K+ATP channels by ATP was also reduced. 7. The reduction of single channel current amplitude during poisoning was attributed to an increase in intracellular Mg2+ concentration caused by a fall in intracellular ATP concentration. These results also show that metabolic poisoning causes direct activation of K+ATP channels in skeletal muscle, and that is activation is at least partially mediated through an increase in intracellular Mg(2+) concentration and a decrease in intracellular pH.
Allard
B
B
Laboratoire de Physiolgie des Eléments Excitables, CNRS URA 180, Université C. Bernard, Villeurbanne France.
Lazdunski
M
M
Rougier
O
O
D019297:2,4-Dinitrophenol; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000963:Antimetabolites / Q000506:poisoning*; D001578:Benzopyrans / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D019806:Cromakalim; D003486:Cyanides / Q000506:poisoning; D004139:Dinitrofluorobenzene / Q000506:poisoning; D004140:Dinitrophenols / Q000506:poisoning; D004594:Electrophysiology; D005905:Glyburide / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008274:Magnesium / Q000502:physiology*; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology; D014475:Uncoupling Agents / Q000506:poisoning
D000963:Antimetabolites; D001578:Benzopyrans; D003486:Cyanides; D004140:Dinitrophenols; D015221:Potassium Channels; D011758:Pyrroles; D014475:Uncoupling Agents; D019806:Cromakalim; D000255:Adenosine Triphosphate; D004139:Dinitrofluorobenzene; D008274:Magnesium; D019297:2,4-Dinitrophenol; D005905:Glyburide