Abstract
The earliest known change in rat fast muscle following denervation is a fall in resting membrane potential unaccompanied by change in membrane resistance. The hypothesis that increased Na permeability (PNa) accounted for this early depolarization was tested. In all experiments, rat extensor digitorum longus muscles were studied in vitro at 25.degree. C. Li uptake in vitro, used as a measure of PNa [partial pressure of Na], was greater in 1- and 2-day denervated muscles (and in 2-day denervated diaphragm) than in paired controls. The extra Li taken up by denervated muscle was not sequestered in an extracellular or freely exchangeable compartment, nor was it irreversibly bound. Measurements of resting membrane potential and of internal Na, K and Li in Krebs solution before and 2 h after replacement of NaCl by LiCl, were used to compute the ratios PNa/PK and PLi/PK for normal or denervated muscles. PNa and PLi were similar relative to PK within each class of muscle. Both PNa/PK and PLi/PK ratios were elevated more than 2-fold in denervated muscle, as were most estimates of relative PLi approximated by the flux equation. 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 results from increased PNa. The Na-K pump of denervated muscle was as sensitive to ouabain as normal muscle. An effect of ouabain on PNa may explain previously noted differential effects of ouabain on normal and denervated muscle.