ACELL February 47/2

Matar, W., T. M. Nosek, D. Wong, and J.-M. Renaud. Pinacidil suppresses contractility and preserves energy but glibenclamide has no effect during muscle fatigue. Am. J. Physiol. Cell Physiol. 278: C404–C416, 2000.—The effects of 10 μM glibenclamide, an ATP-sensitive K1 (KATP) channel blocker, and 100 μM pinacidil, a channel opener, were studied to determine how the KATP channel affects mouse extensor digitorum longus (EDL) and soleus muscle during fatigue. Fatigue was elicited with 200-ms-long tetanic contractions every second. Glibenclamide did not affect rate and extent of fatigue, force recovery, or 86Rb1 fractional loss. The only effects of glibenclamide during fatigue were: an increase in resting tension (EDL and soleus), a depolarization of the cell membrane, a prolongation of the repolarization phase of action potential, and a greater ATP depletion in soleus. Pinacidil, on the other hand, increased the rate but not the extent of fatigue, abolished the normal increase in resting tension during fatigue, enhanced force recovery, and increased 86Rb1 fractional loss in both the EDL and soleus. During fatigue, the decreases in ATP and phosphocreatine of soleus muscle were less in the presence of pinacidil. The glibenclamide effects suggest that fatigue, elicited with intermittent contractions, activates few KATP channels that affect resting tension and membrane potentials but not tetanic force, whereas opening the channel with pinacidil causes a faster decrease in tetanic force, improves force recovery, and helps in preserving energy.