Excitation-induced cell damage and beta2-adrenoceptor agonist stimulated force recovery in rat skeletal muscle.
Intensive exercise leads to a loss of force, which may be long lasting and associated with muscle cell damage. To simulate this impairment and to develop means of compensating the loss of force, extensor digitorum longus muscles from 4-wk-old rats were fatigued using intermittent 40-Hz stimulation (10 s on, 30 s off). After stimulation, force recovery, cell membrane leakage, and membrane potential were followed for 240 min. The 30-60 min of stimulation reduced tetanic force to approximately 10% of the prefatigue level, followed by a spontaneous recovery to approximately 20% in 120-240 min. Loss of force was associated with a decrease in K+ content, gain of Na+ and Ca2+ content, leakage of the intracellular enzyme lactic acid dehydrogenase (10-fold increase), and depolarization (13 mV). Stimulation of the Na+-K+ pump with either the beta2-adrenoceptor agonist salbutamol, epinephrine, rat calcitonin gene-related peptide (rCGRP), or dibutyryl cAMP improved force recovery by 40-90%. The beta-blocker propranolol abolished the effect of epinephrine on force recovery but not that of CGRP. Both spontaneous and salbutamol-induced force recovery were prevented by ouabain. The salbutamol-induced force recovery was associated with repolarization of the membrane potential (12 mV) to the level measured in unfatigued muscles. In conclusion, in muscles exposed to fatiguing stimulation leading to a considerable loss of force, cell leakage, and depolarization, stimulation of the Na+-K+ pump induces repolarization and improves force recovery, possibly due to the electrogenic action of the Na+-K+ pump. This mechanism may be important for the restoration of muscle function after intense exercise.
Mikkelsen
Ulla Ramer
UR
Department of Physiology and Biophysics, University of Aarhus, Arhus, Denmark.
Gissel
Hanne
H
Fredsted
Anne
A
Clausen
Torben
T
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D018343:Receptors, Adrenergic, beta-2; D010042:Ouabain; D012964:Sodium; D011433:Propranolol; D000420:Albuterol; D011188:Potassium; D002118:Calcium; D004837:Epinephrine