Quantal release of acetylcholine does not regulate the resting membrane potential of mammalian skeletal muscle: Evidence from in vivo experiments

Abstract

Soleus muscles of adult rats were denervated by transecting the soleus nerve as it enters the muscle, by transecting the sciatic nerve in the upper thigh, or by transecting spinal nerves L4 to L6. The segment of nerve attached to the muscle was therefore short (1 to 2 mm), intermediate (35 to 37 mm), or long (62 to 64 mm). At various times postoperatively, the muscles were exposed in vivo and resting membrane potentials (RMPs) and miniature end-plate potentials (MEPPs) were recorded at a site within 3 mm of the nerves entrance into the muscle. Bathing the muscles in rat serum containing 10 meq Ca rather than physiologic solution (2 m m Ca) did not alter either the RMP or the amplitude and frequency of the MEPPs. Membrane depolarization was apparent as early as 6 h after transecting the nerve at its entrance into the muscle, and the RMP continued to decline in a linear manner at a rate of 0.48 mV/h. Transecting the nerve farther from its entrance into the muscle produced a delay in the onset of depolarization which was linearly related to the length of the nerve stump. Regardless of the level of nerve transection, the onset of membrane depolarization always preceded any change in transmitter release, but eventually the frequency and amplitude of the MEPPs declined and disappeared. These results confirm established findings in which the RMP and MEPPs were recorded in vitro. We conclude that there is no causal relationship between the decline in transmitter release and the RMP of denervated muscle, that in vitro measurements of membrane properties after denervation are a true reflection of changes occurring in vivo, and that the normal RMP is maintained by a neurotrophic mechanism.