HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 582/2/843    most recent jphysiol.2007.130955v1 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cifelli, C. Articles by Renaud, J.-M. Search for Related Content PubMed PubMed Citation Articles by Cifelli, C. Articles by Renaud, J.-M. Related Collections Skeletal Muscle and Exercise

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

Activation of the K_ATP channels results in faster fatigue rates as the channels depress action potential amplitude, whereas abolishing the channel activity has no effect in whole extensor digitorum longus (EDL) and soleus muscles. In this study, we examined the effects of abolished K_ATP channel activity during fatigue at 37°C on free intracellular Ca²⁺ (Ca²⁺_i) and tetanic force using single muscle fibres and small muscle bundles from the flexor digitorum brevis (FDB). K_ATP channel deficient muscle fibres were obtained (i) pharmacologically by exposing wild-type fibres to glibenclamide, and (ii) genetically using null mice for the Kir6.2 gene (Kir6.2^–/– mice). Fatigue was elicited using 200 ms tetanic contractions every second for 3 min. This study demonstrated for the first time that abolishing K_ATP channel activity at 37°C resulted in faster fatigue rates, where decreases in peak Ca²⁺_i and tetanic force were faster in K_ATP channel deficient fibres than in control wild-type fibres. Furthermore, several contractile dysfunctions were also observed in K_ATP channel deficient muscle fibre. They included partially or completely supercontracted single muscle fibres, greater increases in unstimulated Ca²⁺_i and unstimulated force, and lower force recovery. We propose that the observed faster rate of fatigue in K_ATP channel deficient fibres is because the decreases in peak Ca²⁺_i and force caused by contractile dysfunctions prevail over the expected slower decreases when the channels do not depress action potential amplitude.

(Received 23 February 2007; accepted after revision 10 May 2007; first published online 17 May 2007)
Corresponding author J.-M. Renaud: University of Ottawa, Department of Cellular and Molecular Medicine, 451 Smyth Rd, Ottawa, Ontario, Canada, K1H 8M5. Email: jmrenaud{at}uottawa.ca

This article has been cited by other articles:

				D. Tricarico, A. Mele, G. M. Camerino, A. Laghezza, G. Carbonara, G. Fracchiolla, P. Tortorella, F. Loiodice, and D. C. Camerino Molecular Determinants for the Activating/Blocking Actions of the 2H-1,4-Benzoxazine Derivatives, a Class of Potassium Channel Modulators Targeting the Skeletal Muscle KATP Channels Mol. Pharmacol., July 1, 2008; 74(1): 50 - 58. [Abstract] [Full Text] [PDF]

				M. J. McKenna, J. Bangsbo, and J.-M. Renaud Muscle K+, Na+, and Cl disturbances and Na+-K+ pump inactivation: implications for fatigue J Appl Physiol, January 1, 2008; 104(1): 288 - 295. [Abstract] [Full Text] [PDF]