Electrical stimulation of denervated muscles reduces incorporation of methionine into the ACh receptor

Abstract

ONCE a neuromuscular synapse has formed, the density of acetylcholine (ACh) receptors in the subsynaptic muscle membrane remains relatively constant, even after denervation of the muscle¹. In contrast, the density of ACh receptors in the extrajunctional muscle membrane can vary widely. Extrajunctional receptors are present at high density in developing muscle, but are reduced to low levels during maturation of muscle fibres². Their number is increased after denervation in the adult^3,4, and is again decreased on subsequent re-innervation of the muscle⁵. Several experiments have demonstrated that the amount and pattern of muscle activity strongly influence the density of extrajunctional ACh receptors (for review, see ref. 6), although other factors may be important as well^6–9. Because extrajunctional receptors undergo continual turnover in the membrane^10–12, the effect of changes in activity on their density could result from alteration in rates of receptor synthesis or degradation. Recent experiments have shown that the reduction of receptor levels caused by stimulation in organ culture is accompanied by a decrease in the rate of receptor degradation¹³. These results imply that activity decreases the rate of receptor synthesis or its insertion into the membrane. In direct support of this idea, we report that electrical stimulation of denervated muscle reduces incorporation of ³⁵S-methionine into ACh receptors.