Cation movements in normal and short-term denervated rat fast twitch muscle.

1. The earliest known change in rat fast muscle following denervation is a fall in resting membrane potential unaccompanied by change in membrane resistance. The present study tested the hypothesis that increased Na permeability (P(Na)) accounted for this early depolarization.2. In all experiments, rat extensor digitorum longus muscles were studied in vitro at 25 degrees C. Li uptake in vitro, used as a measure of P(Na), was greater in 1- and 2-day denervated muscles (and in 2-day denervated diaphragm) than in paired controls.3. The extra Li taken up by denervated muscle was not sequestered in an extracellular or freely exchangeable compartment, nor was it irreversibly bound.4. Measurements of resting membrane potential and of internal Na, K, and Li in Krebs solution before and 2 hr after replacement of NaCl by LiCl, were used to compute the ratios P(Na)/P(K) and P(Li)/P(K) for normal or denervated muscles. P(Na) and P(Li) were similar relative to P(K) within each class of muscle.5. Both P(Na)/P(K) and P(Li)/P(K) ratios were elevated more than twofold in denervated muscle, as were most estimates of relative P(Li) approximated by the flux equation.6. These data, and measurement of resting membrane potential of normal muscle in 1 mM external K-Krebs solution, support the view that an electrogenic Na-K pump does not substantially contribute to this potential of normal or denervated muscle, and that the early depolarization after denervation results from increased P(Na).7. The Na-K pump of denervated muscle was as sensitive to ouabain as normal muscle. An effect of ouabain on P(Na) may explain previously noted differential effects of ouabain on normal and denervated muscle.