Aconitine-induced increase and decrease of acetylcholine release in the mouse phrenic nerve-hemidiaphragm muscle preparation.
The effect of aconitine on acetylcholine (ACh) release from motor nerve terminals in the mouse phrenic nerve-diaphragm muscle preparation was studied by a radioisotope method. Both electrical stimulation-evoked release and spontaneous release of 3H-ACh from the preparation preloaded with 3H-choline were measured. The change in the muscle tension was simultaneously recorded in the same preparation. Aconitine (0.1 microM) increased electrically evoked 3H-ACh release, while at higher concentrations (0.3-3 microM) it decreased the evoked release and muscle tension. High concentrations of aconitine (3-30 microM) caused a concentration-dependent increase in spontaneous 3H-ACh release. All these effects were suppressed by tetrodotoxin. The aconitine-induced spontaneous release consisted of two different components: a Ca(2+)-dependent phasic release that was inactivated within a few minutes and a Ca(2+)-independent, long lasting release at a low level. The depression of the Ca(2+)-dependent quantal release seems attributable to the decline of Ca2+ influx into the nerve rather than inactivation of sodium channels. We conclude that aconitine increases and then decreases electrical stimulation-evoked ACh release from the motor nerve through prolonged activation of sodium channels. Further activation of the channels enhances spontaneous release and the subsequent complete inactivation of the quantal release may be due to block of Ca2+ influx.
Okazaki
M
M
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Kimura
I
I
Kimura
M
M
D000109:Acetylcholine / Q000378:metabolism*; D000157:Aconitine / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002794:Choline / Q000378:metabolism; D003964:Diaphragm / Q000187:drug effects / Q000378:metabolism*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010791:Phrenic Nerve / Q000187:drug effects / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D013779:Tetrodotoxin; D002794:Choline; D000109:Acetylcholine; D002118:Calcium; D000157:Aconitine