Antagonism by tubocurarine and verapamil of the regenerative acetylcholine release from mouse motor nerve.
The role of presynaptic acetylcholine receptors and Ca2+ channels in the regenerative acetylcholine release was studied in the cut muscle preparation of mouse phrenic nerve hemidiaphragm. The regenerative release shown as a prolonged endplate depolarization was evoked by stimulation of the nerve with a train of pulse at 75-300 Hz when acetylcholinesterase activity was depressed with neostigmine or by lowering temperature. Tubocurarine, cobratoxin, verapamil, diltiazem and nifedipine at low concentrations, which had a negligible effect on the endplate potential, shortened the duration of regenerative depolarization while leaving the amplitude unaffected. In contrast, Mn2+ at concentrations that markedly reduced the amplitude of single endplate potentials caused little suppression of the regenerative depolarization though intensive stimulation was needed to trigger the response. On the other hand, atropine inhibited the regenerative depolarization only at high concentrations which also depressed endplate potentials. These results indicate that the mechanism for evoking the regenerative release involves the activation of acetylcholine receptors and Ca2+ channels which are sensitive to tubocurarine and Ca2+ channel blockers. The Ca2+ channel concerned, however, appears to differ from that involved in the normal quantal release of acetylcholine.
Hong
S J
SJ
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, R.O.C.
Chang
C C
CC
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D008813:Mice, Inbred ICR; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism*; D009416:Nerve Regeneration / Q000187:drug effects*; D010791:Phrenic Nerve / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000187:drug effects; D014403:Tubocurarine / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D011978:Receptors, Nicotinic; D001285:Atropine; D014700:Verapamil; D000109:Acetylcholine; D014403:Tubocurarine