BLOCKING ATP-SENSITIVE K+ CHANNEL DURING METABOLIC INHIBITION IMPAIRSMUSCLE CONTRACTILITY

The objectives of this study were to determine the metabolic condition s 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 mu M) 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 microelectr odes. Tetanic and resting tension were measured with a force transduce r. 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 membra ne conductance. When glibenclamide was added 60 min before metabolic i nhibition, the decrease in tetanic force was faster than in control mu scle (no glibenclamide). This faster decrease in tetanic force was ass ociated with significant membrane depolarizations, greater increases i n resting tension, greater depletions of ATP and PCr contents, and gre ater increases in ADP content. Addition of glibenclamide 8 min into me tabolic inhibition caused an increase in tetanic force followed by a f aster 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 I) wer e activated during metabolic inhibition and 2) contributed to the decr ease in tetanic force but also 3) had a myoprotective effect protectin g skeletal muscle against muscle function impairment.