{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T02:44:22Z","timestamp":1698720262360},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,2,21]],"date-time":"2005-02-21T00:00:00Z","timestamp":1108944000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2005,3]]},"abstract":"<jats:p>Intense exercise results in increases in intracellular Na<jats:sup>+<\/jats:sup> and extracellular K<jats:sup>+<\/jats:sup> 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<jats:sup>+<\/jats:sup> and K<jats:sup>+<\/jats:sup> 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\u2010fold increase in Na<jats:sup>+<\/jats:sup> influx that was tetrodotoxin (TTX) insensitive, but abolished by tubocurarine, resulting in a significant 36% increase in intracellular Na<jats:sup>+<\/jats:sup>, and 8% decrease in intracellular K<jats:sup>+<\/jats:sup> 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 \u221273 \u00b1 1 to \u221260 \u00b1 1 mV compared with \u221264 \u00b1 1 mV. Carbacholine (10<jats:sup>\u22124<\/jats:sup><jats:sc>m<\/jats:sc>) significantly reduced tetanic force to 31 \u00b1 3% of controls, which underwent significant recovery upon application of Na<jats:sup>+<\/jats:sup>\u2013K<jats:sup>+<\/jats:sup> pump stimulators: salbutamol (10<jats:sup>\u22125<\/jats:sup><jats:sc>m<\/jats:sc>), adrenaline (10<jats:sup>\u22125<\/jats:sup><jats:sc>m<\/jats:sc>) and calcitonin gene\u2010related peptide (CGRP; 10<jats:sup>\u22127<\/jats:sup><jats:sc>m<\/jats:sc>). The force recovery with salbutamol was accompanied by a recovery of intracellular Na<jats:sup>+<\/jats:sup> and K<jats:sup>+<\/jats:sup> contents, and a small but significant 4\u20135 mV recovery of membrane potential. Similar results were obtained using succinylcholine (10<jats:sup>\u22124<\/jats:sup><jats:sc>m<\/jats:sc>), indicating that Na<jats:sup>+<\/jats:sup>\u2013K<jats:sup>+<\/jats:sup> pump stimulation may prevent or restore succinylcholine\u2010induced hyperkalaemia. The stimulation of the Na<jats:sup>+<\/jats:sup>\u2013K<jats:sup>+<\/jats:sup> pump allows muscle to partially recover contractility by regaining excitability through electrogenically driven repolarization of the muscle membrane.<\/jats:p>","DOI":"10.1113\/jphysiol.2004.080390","type":"journal-article","created":{"date-parts":[[2005,1,14]],"date-time":"2005-01-14T01:18:39Z","timestamp":1105665519000},"page":"459-469","source":"Crossref","is-referenced-by-count":12,"title":["Na<sup>+<\/sup>\u2013K<sup>+<\/sup> pump stimulation restores carbacholine\u2010induced loss of excitability and contractility in rat skeletal muscle"],"prefix":"10.1113","volume":"563","author":[{"given":"W. A.","family":"Macdonald","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"O. 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