Further studies on the control of ACh sensitivity by muscle activity in the rat.

Abstract

1. Denervated rat soleus muscles were stimulated directly through chronically implanted electrodes and the influence of different amounts and patterns of stimuli on the acetylcholine (ACh) sensitivity of the muscle was studied. The number of stimuli was varied by giving similar trains of stimuli (10 Hz for 10 sec) at different intervals (0 to 12 hr). The pattern of stimulation was varied by giving different trains of stimuli (100 Hz for 1 sec, 10 Hz for 10 sec and 1 Hz continuously) as the same average frequency of stimulation (1 Hz). 2. Stimulation usually started 5 days after the denervation when ACh hypersensitivity was fully developed. Most stimulation procedures reduced extrajunctional ACh sensitivity to normal or below normal values within 5‐21 days, and these levels were maintained on prolonged stimulation. 3. The rate at which ACh hypersensitivity disappeared increased with increasing amount and frequency of stimulation. However, as few as 100 stimuli given every 5‐5 hr for 3 weeks caused a tenfold reduction of sensitivity. 4. The stimulation had little or no effect on the ACh sensitivity at the end plate. Along the rest of the fibre the sensitivity was reduced at approximately the same rate except near the tendons where it appeared to fall more slowly in some fibres. 5. The stimulation restored the resting membrane potential of the denervated fibres to normal.

Prolongation of Evoked and Spontaneous Synaptic Currents at the Neuromuscular Junction after Activity Blockade Is Caused by the Upregulation of Fetal Acetylcholine Receptors

“…The effect of extrajunctional fetal-type AChRs on synaptic function that we report here may have implications for synaptic transmission early in reinnervation when the safety factor is low. Denervated muscle has high levels of extrajunctional AChRs (Hartzell and Fambrough, 1972;Lomo and Rosenthal, 1972;Lomo and Westgaard, 1975), and at early times during reinnervation of muscle, there is prolongation of EPC decay (Argentieri et al, 1992). Given our findings, it appears likely that prolongation of EPCs after reinnervation is attributable to the presence of extrajunctional AChRs.…”

“…In these muscles, AChRs are located almost exclusively within NMJs; very few AChRs are present on muscle membrane outside of the endplate (Hartzell and Fambrough, 1972;Lomo and Rosenthal, 1972). An extended blockade of neuromuscular activity triggers what appears to be a homeostatic increase in postsynaptic expression of AChRs (Hartzell and Fambrough, 1972;Lomo and Rosenthal, 1972;Lomo and Westgaard, 1975). These upregulated AChRs are of a different type than the AChRs normally present in mature muscle and contain the ␣(2), ␤, ␦, and ␥ subunits (fetal-type AChRs) (Witzemann et al, 1987;Kues et al, 1995).…”

Propriétés des fibres musculaires squelettiques. 1. Influence de l'innervation motrice

“…Ces modifications peuvent être la conséquence des perturbations observées au niveau des plaques motrices (Vincent-Ablazey et al, 1978;Dias, 1979 ;McLachlan, 1983) ou des modifications de la vitesse de conduction des axones innervant les fibres affectées (Russel, 1980). Enfin, contrairement à la dénervation, on n'observe pas de sensibilité extrajonctionnelle à l'acétylcholine, ce phénomène n'apparaissant que de façon transitoire dans les fibres ténotomisées (Fischbach et Robbins, 1971 Lewis, 1965b;Eccles, 1967 (Dubowitz, 1967a, b;Robbins et al, 1969; Salafsky, 1970;Romanul, 1971 (Koenig, 1967(Koenig, , 1970Zelena et al, 1967 ;Bennett et al, 1973 ; Rosenthal, 1972 ;Lomo et Westgaard, 1975Westgaard, , 1976 ; b) les propriétés contractiles lentes et rapides des muscles (L 0 mo etal., 1974) ; c) la formation de synapses ectopiques par un nerf étranger supplémentaire (Jansen et al, 1973;Lomo et Slater, 1978) Salmons, 1981 ;Sarzala et al, 1982). Parallèlement, la densité de capillaires, le nombre, ainsi que la taille des mitochondries, augmentent (Cotter et al, 1973 ;Salmons et al, 1978 ;Reichmann et al, 1985).…”

Mechanisms of Neuromuscular Dysfunction in Critical Illness

“…Evidence for this comes from experiments in which restoring muscle activity of denervated muscle prevented loss of resting potential [50,51]. This is important clinically because it suggests that depolarization of resting potential will occur whenever muscle is inactive.…”