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This Article Full Text Full Text (PDF) All Versions of this Article: 93/10/1126    most recent expphysiol.2008.042572v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Cifelli, C. Articles by Renaud, J.-M. PubMed PubMed Citation Articles by Cifelli, C. Articles by Renaud, J.-M. Related Collections Human, Environmental & Exercise Muscle

¹ University of Ottawa, Department of Cellular and Molecular Medicine, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5

Muscles deficient in ATP-dependent potassium (K_ATP) channels develop contractile dysfunctions during fatigue that may explain their apparently faster rate of fatigue compared with wild-type muscles. The objectives of this study were to determine: (1) whether the contractile dysfunctions, namely unstimulated force and depressed force recovery, result from excessive membrane depolarization and Ca²⁺ influx through L-type Ca²⁺ channels; and (2) whether reducing the magnitude of these two contractile dysfunctions reduces the rate of fatigue in K_ATP channel-deficient muscles. To reduce Ca²⁺ influx, we lowered the extracellular Ca²⁺ concentration ([Ca²⁺]_o) from 2.4 to 0.6 mM or added 1 µM verapamil, an L-type Ca²⁺ channel blocker. Flexor digitorum brevis (FDB) muscles deficient in K_ATP channels were obtained by exposing wild-type muscles to 10 µM glibenclamide or by using FDB from Kir6.2^–/– mice. Fatigue was elicited with one contraction per second for 3 min at 37°C. In wild-type FDB, lowered [Ca²⁺]_o or verapamil did not affect the decrease in peak tetanic force and unstimulated force during fatigue and force recovery following fatigue. In K_ATP channel-deficient FDB, lowered [Ca²⁺]_o or verapamil slowed down the decrease in peak tetanic force recovery, reduced unstimulated force and improved force recovery. In Kir6.2^–/– FDB, the rate of fatigue became slower than in wild-type FDB in the presence of verapamil. The cell membrane depolarized from –83 to –57 mV in normal wild-type FDB. The depolarizations in some glibenclamide-exposed fibres were similar to those of normal FDB, while in other fibres the cell membrane depolarized to –31 mV in 80 s, which was also the time when these fibres supercontracted. It is concluded that: (1) K_ATP channels are crucial in preventing excessive membrane depolarization and Ca²⁺ influx through L-type Ca²⁺ channels; and (2) they contribute to the decrease in force during fatigue.

(Received 4 March 2008; accepted after revision 5 June 2008; first published online 27 June 2008)
Corresponding author J.-M. Renaud: University of Ottawa, Department of Cellular and Molecular Medicine, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5. Email: jmrenaud{at}uottawa.ca