title: Extracellular Ca2+-induced force restoration in K+-depressed skeletal muscle of the mouse involves an elevation of [K+]i: implications for fatigue.
abstract: We examined whether a Ca(2+)-K(+) interaction was a potential mechanism operating during fatigue with repeated tetani in isolated mouse muscles. Raising the extracellular Ca(2+) concentration ([Ca(2+)]o) from 1.3 to 10 mM in K(+)-depressed slow-twitch soleus and/or fast-twitch extensor digitorum longus muscles caused the following: 1) increase of intracellular K(+) activity by 20-60 mM (raised intracellular K(+) content, unchanged intracellular fluid volume), so that the K(+)-equilibrium potential increased by ∼10 mV and resting membrane potential repolarized by 5-10 mV; 2) large restoration of action potential amplitude (16-54 mV); 3) considerable recovery of excitable fibers (∼50% total); and 4) restoration of peak force with the peak tetanic force-extracellular K(+) concentration ([K(+)]o) relationship shifting rightward toward higher [K(+)]o. Double-sigmoid curve-fitting to fatigue profiles (125 Hz for 500 ms, every second for 100 s) showed that prior exposure to raised [K(+)]o (7 mM) increased, whereas lowered [K(+)]o (2 mM) decreased, the rate and extent of force loss during the late phase of fatigue (second sigmoid) in soleus, hence implying a K(+) dependence for late fatigue. Prior exposure to 10 mM [Ca(2+)]o slowed late fatigue in both muscle types, but was without effect on the extent of fatigue. These combined findings support our notion that a Ca(2+)-K(+) interaction is plausible during severe fatigue in both muscle types. We speculate that a diminished transsarcolemmal K(+) gradient and lowered [Ca(2+)]o contribute to late fatigue through reduced action potential amplitude and excitability. The raised [Ca(2+)]o-induced slowing of fatigue is likely to be mediated by a higher intracellular K(+) activity, which prolongs the time before stimulation-induced K(+) efflux depolarizes the sarcolemma sufficiently to interfere with action potentials.
authors.affiliation: Sports Performance Research Institute New Zealand, School of Sport and Recreation, Faculty of Health and Environmental Sciences, AUT University, Auckland, New Zealand; Health and Rehabilitation Research Institute, Faculty of Health and Environmental Sciences, AUT University, Auckland, New Zealand; simeon.cairns@aut.ac.nz.
authors.forename: Simeon P
authors.initials: SP
authors.lastname: Cairns
authors.affiliation: Department of Medicine, University of Otago, Dunedin, New Zealand; Department of Physiology, University of Otago, Dunedin, New Zealand;
authors.forename: John P
authors.initials: JP
authors.lastname: Leader
authors.affiliation: Department of Physiology, School of Medical Sciences, University of Auckland, Auckland, New Zealand; Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand; and.
authors.forename: Denis S
authors.initials: DS
authors.lastname: Loiselle
authors.affiliation: Department of Cellular and Molecular Medicine, Center for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Amanda
authors.initials: A
authors.lastname: Higgins
authors.affiliation: Department of Cellular and Molecular Medicine, Center for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Wei
authors.initials: W
authors.lastname: Lin
authors.affiliation: Department of Cellular and Molecular Medicine, Center for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Renaud
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005260:Female; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000502:physiology; D018763:Muscle Fatigue / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000502:physiology*; D011188:Potassium / Q000378:metabolism*; D012508:Sarcolemma / Q000378:metabolism / Q000502:physiology
chemical_list: D011188:Potassium; D002118:Calcium
keywords: action potential; calcium; excitability; fiber-type; muscle fatigue; potassium