title: Na+-K+ pump stimulation restores carbacholine-induced loss of excitability and contractility in rat skeletal muscle.
abstract: Intense exercise results in increases in intracellular Na+ and extracellular K+ concentrations, leading to depolarization and a loss of muscle excitability and contractility. Here, we use carbacholine to chronically activate the nicotinic acetylcholine (nACh) receptors to mimic the changes in membrane permeability, chemical Na+ and K+ gradients and membrane potential observed during intense exercise. Intact rat soleus muscles were mounted on force transducers and stimulated electrically to evoke short tetani at regular intervals. Carbacholine produced a 2.6-fold increase in Na+ influx that was tetrodotoxin (TTX) insensitive, but abolished by tubocurarine, resulting in a significant 36% increase in intracellular Na+, and 8% decrease in intracellular K+ content. The mid region, near the motor end plate, had much larger alterations than the more distal regions of the muscle, and showed a larger membrane depolarization from -73 +/- 1 to -60 +/- 1 mV compared with -64 +/- 1 mV. Carbacholine (10(-4) M) significantly reduced tetanic force to 31 +/- 3% of controls, which underwent significant recovery upon application of Na+-K+ pump stimulators: salbutamol (10(-5) M), adrenaline (10(-5) M) and calcitonin gene-related peptide (CGRP; 10(-7) M). The force recovery with salbutamol was accompanied by a recovery of intracellular Na+ and K+ contents, and a small but significant 4-5 mV recovery of membrane potential. Similar results were obtained using succinylcholine (10(-4) M), indicating that Na+-K+ pump stimulation may prevent or restore succinylcholine-induced hyperkalaemia. The stimulation of the Na+-K+ pump allows muscle to partially recover contractility by regaining excitability through electrogenically driven repolarization of the muscle membrane.
authors.affiliation: Institute of Physiology and Biophysics, University of Aarhus, DK-8000, Arhus C, Denmark. wmd@fi.au.dk
authors.forename: W A
authors.initials: WA
authors.lastname: Macdonald
authors.forename: O B
authors.initials: OB
authors.lastname: Nielsen
authors.forename: T
authors.initials: T
authors.lastname: Clausen
mesh_terms: D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D018679:Cholinergic Agonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000502:physiology*; D011188:Potassium / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology*; D013390:Succinylcholine / Q000494:pharmacology
chemical_list: D018679:Cholinergic Agonists; D002217:Carbachol; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D013390:Succinylcholine; D011188:Potassium