Carbachol and acetylcholine delay the early postdenervation depolarization of muscle fibres through M1-cholinergic receptors.
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.
Urazaev
A
A
Kazan State Medical University, Russian Federation.
Naumenko
N
N
Malomough
A
A
Nikolsky
E
E
Vyskocil
F
F
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001115:Arecoline / Q000031:analogs & derivatives* / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D046508:Culture Techniques; D003964:Diaphragm / Q000294:innervation / Q000648:ultrastructure; D008297:Male; D008564:Membrane Potentials; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009121:Muscle Denervation; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D010095:Oxotremorine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic / Q000502:physiology*
D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D010880:Piperidines; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic; C015000:arecaidine esters; D010890:Pirenzepine; D001115:Arecoline; D010095:Oxotremorine; D001285:Atropine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D002217:Carbachol; D000109:Acetylcholine