Blocking ATP-sensitive K+ channel during metabolic inhibition impairs muscle contractility.
The objectives of this study were to determine the metabolic conditions in which ATP-sensitive K+ channels (K+(ATP) channels) contribute to a decrease in force. Sartorius muscles of the frog Rana pipiens were subjected to a 60-min metabolic inhibition by exposing them to cyanide (2 mM) and iodoacetate (1 mM). Muscles were exposed to glibenclamide (100 microM) to block K+ATP channels either 60 min before or 8 or 18 min into metabolic inhibition. Resting potentials, action potentials, and membrane conductance were measured using intracellular microelectrodes. Tetanic and resting tension were measured with a force transducer. ATP, ADP, and phosphocreatine (PCr) were measured by high-pressure liquid chromatography. Glibenclamide completely blocked the shortening of action potential but only partially blocked the increase in membrane conductance. When glibenclamide was added 60 min before metabolic inhibition, the decrease in tetanic force was faster than in control muscle (no glibenclamide). This faster decrease in tetanic force was associated with significant membrane depolarizations, greater increases in resting tension, greater depletions of ATP and PCr contents, and greater increases in ADP content. Addition of glibenclamide 8 min into metabolic inhibition caused an increase in tetanic force followed by a faster decrease compared with control. Addition of glibenclamide 18 min into metabolic inhibition had no effect on the tetanic force compared with control muscles. The data indicate that K+ATP channels 1) were activated during metabolic inhibition and 2) contributed to the decrease in tetanic force but also 3) had a myoprotective effect protecting skeletal muscle against muscle function impairment.
Gramolini
A
A
Department of Physiology, University of Ottawa, Ontario, Canada.
Renaud
J M
JM
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D005905:Glyburide / Q000494:pharmacology*; D066298:In Vitro Techniques; D007461:Iodoacetates / Q000494:pharmacology*; D019807:Iodoacetic Acid; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D018763:Muscle Fatigue; D018482:Muscle, Skeletal / Q000502:physiology*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D011894:Rana pipiens; D012966:Sodium Cyanide / Q000494:pharmacology*; D013997:Time Factors
D007461:Iodoacetates; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012966:Sodium Cyanide; D005905:Glyburide; D019807:Iodoacetic Acid