Sodium influx during action potential in innervated and denervated rat skeletal muscles

Resting Na + influx (J i Na ) was measured in innervated and denervated (1–6 days) rat extensor digitorum longus muscle in the absence and presence of 2 μmol/L tetrodotoxin (TTX).The mean value of Na + permeability (P Na ) in innervated muscles was 49.6 ± 2.6 pm.s −1 . At the second day postdenervation, it decreased by about 45%. This was followed, between the second and fourth days, by a sharp rise, which by the sixth day reached a steady value ∼2.5 times greater than that of innervated muscles. This, most likely, generated the 30% increase in internal [Na + ] concentration ([Na + ] I ) observed at this time. Tetrodotoxin reduced P Na of both innervated and denervated muscles by about 25%. In 6‐day denervated muscles, virtually all the TTX effect on P Na represents the blockage of TTX‐resistant Na + channels. Denervation produced a depolarization of about 20 mV by the sixth day. The extra J i Na per action potential (AP) decreased monotonically with time after denervation from 20.0 ± 3.8 in innervated to 11.1 ± 1.0 nmol.g −1 .AP −1 in 6‐day denervated muscles. The overshoot of the AP decreased from 15 ± 1 in innervated to 7 ± 1 mV in 6‐day denervated muscles. Likewise, the maximum rate of rise (+dV/dt), an expression of the inward Na + current, fell from 305 ± 14 in innervated to 188 ± 18 V.s −1 in 6‐day denervated muscles. The estimated 6‐day denervated/innervated ratio of peak Na + conductance (g Na ) was 0.67. The changes in AP parameters promoted by denervation were substantially reduced when both innervated and denervated fibers were hyperpolarized to −90 mV. These results suggest that the depolarization, mainly due to the increase in P Na /P K ratio, increases Na + inactivation and consequently reduces peak g Na , in spite of the absolute increment in resting TTX‐sensitive P Na . This, in addition to the moderate reduction in the inward driving force on Na + , decreases the inward Na + current and the extra J i Na per AP. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 1026–1033, 2001