Control of end-plate channel properties by neurotrophic effects and by muscle activity in rat

1. The formation of ectopic neuromuscular synapses was induced in rat soleus muscle by implantation of the fibular nerve into the proximal part of the muscle and subsequent sectioning of the soleus nerve. The gating properties of acetylcholine (ACh) receptors at the newly formed end-plates were examined by analysis of acetylcholine-induced membrane current fluctuations. 2. In agreement with earlier studies, the apparent mean open time of end-plate channels decreased during synaptic development from about 4 ms to about 1 ms (-60 mV membrane potential, 22 degrees C) within 7-18 days after the soleus nerve had been cut. 3. When the fibular nerve was cut at an early stage of end-plate development, fast-gating channels with apparent mean open times of 1 ms characteristic of mature end-plates did not develop within the next 10-14 days. 4. When the fibular nerve was cut at an early stage of end-plate development and the soleus muscle was then stimulated chronically via implanted electrodes, fast-gating channels did develop in the absence of the nerve terminals within 4-6 days. 5. When impulse conduction in the transplanted fibular nerve was blocked chronically at the time of soleus nerve section such that ectopic end-plates formed in inactive muscle, fast-gating channels developed within 12-14 days. 6. The results show that motoneurones control the conversion from slow-gating fetal to fast-gating adult-type ACh receptor channels at ectopic end-plates in rat soleus muscles. The conversion occurs in the absence of impulse activity provided the nerve continues to be present. However, it also occurs in the absence of the nerve provided the muscle is active and had received an early priming influence from the nerve. Thus, nerve-evoked muscle activity and nerve-released trophic influences complement each other in controlling the gating properties of junctional ACh receptor channels.