ABSTRACT
The resting membrane potential (RMP) of denervated muscle fibres of rat diaphragm muscle is depolarized by approximately 8-10 mV during the first 3 h after nerve section and this early postdenervation depolarization is reduced substantially by the presence of 5x10(-8) M acetylcholine (ACh) or carbachol (CB). The muscarinic antagonist atropine (Atr; 5x10(-9) to 5x10(-6) M) reduced the effect of CB in a dose-dependent manner (K(i)=7x10(-8) M) and increased the rate of the early postdenervation depolarization. In lower doses (5x10(-7) M), Atr acted only in the presence of an allosteric stabilizator hexamethylene-bis-[dimethyl-(3-phtalimidopropyl)ammonium] (W-84). Also pirenzepine, a specific inhibitor of the M1 subtype of muscarinic receptor, blocked the action of CB in a dose-dependent manner with an apparent inhibition constant K(i)=1x10(-7) microM. DAMP, a specific M3 antagonist, was without effect on the muscle hyperpolarization induced by CB. CB also hyperpolarized the membrane potentials of muscles which were denervated for 1-3 days. It is concluded that ACh and CB protect the muscle fibres from early depolarization through M1-cholinergic receptors on the muscle membrane. These particular receptors can apparently mediate the 'trophic', non-impulse regulation of RMP in skeletal muscles when they are activated by acetylcholine released non-quantally.
