The effects of the ATP-sensitive K+ channel (KATP channel) opener cromakalim on excitation-contraction (E-C) coupling were studied in skeletal muscle during fatiguing and non-fatiguing activity. Intracellular calcium concentration ([Ca2+]i) was monitored using the fluorescent indicator fura-2 in isolated single skeletal muscle fibres enzymatically dissociated from rat flexor digitorum brevis. A protocol of tetanic stimulation (50 Hz for 300 ms) with progressively shorter durations between tetani was used to induce E-C coupling failure in these cells. Cromakalim (100-800 microM) had little effect on peak [Ca2+]i during twitch and non-fatiguing tetanic stimulation. However, with 0.4 s between tetani, 100 microM cromakalim decreased peak tetanic [Ca2+]i from 1.47 +/- 0.11 microM to 8.35 +/- 55 nM, but did not affect resting [Ca2+]i (control, 220 +/- 40 nM; with cromakalim, 171 +/- 33 nM). Cyanide (2 mM) decreased tetanic [Ca2+]i and increased resting [Ca2+]i during the stimulus protocol; with 0.4 s between tetani, peak [Ca2+]i was 820 +/- 50 nM and resting [Ca2+]i was 443 +/- 32 nM. The ability of cromakalim to inhibit E-C coupling was enhanced by the presence of cyanide. Complete blockade of metabolism by cyanide and iodoactetate (0.1 mM) caused a marked rise in resting [Ca2+]i and inhibition of the tetanic rise of [Ca2+]i. With cromakalim (100 microM) present, E-C coupling failed during metabolic blockade but without a significant increase in resting [Ca2+]i. These results are consistent with a role for the KATP channel in the failure of Ca2+ release during fatigue.

This article has been cited by other articles:

				C. Cifelli, L. Boudreault, B. Gong, J.-P. Bercier, and J.-M. Renaud Contractile dysfunctions in ATP-dependent K+ channel-deficient mouse muscle during fatigue involve excessive depolarization and Ca2+ influx through L-type Ca2+ channels Exp Physiol, October 1, 2008; 93(10): 1126 - 1138. [Abstract] [Full Text] [PDF]

				C. Cifelli, F. Bourassa, L. Gariepy, K. Banas, M. Benkhalti, and J.-M. Renaud KATP channel deficiency in mouse flexor digitorum brevis causes fibre damage and impairs Ca2+ release and force development during fatigue in vitro J. Physiol., July 15, 2007; 582(2): 843 - 857. [Abstract] [Full Text] [PDF]

				M. Thabet, T. Miki, S. Seino, and J.-M. Renaud Treadmill running causes significant fiber damage in skeletal muscle of KATP channel-deficient mice Physiol Genomics, July 14, 2005; 22(2): 204 - 212. [Abstract] [Full Text] [PDF]

				B. Gong, D. Legault, T. Miki, S. Seino, and J. M. Renaud KATP channels depress force by reducing action potential amplitude in mouse EDL and soleus muscle Am J Physiol Cell Physiol, December 1, 2003; 285(6): C1464 - C1474. [Abstract] [Full Text] [PDF]

				W. Matar, J. A. Lunde, B. J. Jasmin, and J.-M. Renaud Denervation enhances the physiological effects of the KATP channel during fatigue in EDL and soleus muscle Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2001; 281(1): R56 - R65. [Abstract] [Full Text] [PDF]

				B. Gong, T. Miki, S. Seino, and J. M. Renaud A KATP channel deficiency affects resting tension, not contractile force, during fatigue in skeletal muscle Am J Physiol Cell Physiol, November 1, 2000; 279(5): C1351 - C1358. [Abstract] [Full Text] [PDF]

				N. G. MacFarlane, G. M. Darnley, and G. L. Smith Cellular basis for contractile dysfunction in the diaphragm from a rabbit infarct model of heart failure Am J Physiol Cell Physiol, April 1, 2000; 278(4): C739 - C746. [Abstract] [Full Text] [PDF]