Na+-K+ pump stimulation restores carbacholine-induced loss of excitability and contractility in rat skeletal muscle.

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.