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Na + –K + pump stimulation restores carbacholine‐induced loss of excitability and contractility in rat skeletal muscle
Author(s) -
Macdonald W. A.,
Nielsen O. B.,
Clausen T.
Publication year - 2005
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2004.080390
Subject(s) - depolarization , contractility , chemistry , tetrodotoxin , intracellular , acetylcholine , membrane potential , biophysics , extracellular , stimulation , medicine , tetanic stimulation , endocrinology , biochemistry , biology , neurotransmission , receptor
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.