Protective role of extracellular chloride in fatigue of isolated mammalian skeletal muscle

1 Division of Sport and Recreation, Auckland University of Technology, Auckland 1020; 2 Department of Physiology, School of Medicine, University of Auckland, Auckland 92019, New Zealand; and 3 Department of Cellular and Molecular Medicine, Neuromuscular Research Center, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5 Submitted 31 December 2003 ; accepted in final form 11 May 2004 A possible role of extracellular Cl – concentration ([Cl – ] o ) in fatigue was investigated in isolated skeletal muscles of the mouse. When [Cl – ] o was lowered from 128 to 10 mM, peak tetanic force was unchanged, fade was exacerbated (wire stimulation electrodes), and a hump appeared during tetanic relaxation in both nonfatigued slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles. Low [Cl – ] o increased the rate of fatigue 1 ) with prolonged, continuous tetanic stimulation in soleus, 2 ) with repeated intermittent tetanic stimulation in soleus or EDL, and 3 ) to a greater extent with repeated tetanic stimulation when wire stimulation electrodes were used rather than plate stimulation electrodes in soleus. In nonfatigued soleus muscles, application of 9 mM K + with low [Cl – ] o caused more rapid and greater tetanic force depression, along with greater depolarization, than was evident at normal [Cl – ] o . These effects of raised [K + ] o and low [Cl – ] o were synergistic. From these data, we suggest that normal [Cl – ] o provides protection against fatigue involving high-intensity contractions in both fast- and slow-twitch mammalian muscle. This phenomenon possibly involves attenuation of the depolarization caused by stimulation- or exercise-induced run-down of the transsarcolemmal K + gradient. potassium; skeletal muscle contraction; membrane potential; myotonia Address for reprint requests and other correspondence: S. P. Cairns, Division of Sport and Recreation, Auckland Univ. of Technology, Private Bag 92006, Auckland 1020, New Zealand (E-mail: simeon.cairns{at}aut.ac.nz ).