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 nerv e terminals in the mouse phrenic nerve-diaphragm muscle preparation wa s studied by a radioisotope method. Both electrical stimulation-evoked release and spontaneous release of H-3-ACh from the preparation prelo aded with H-3-choline were measured. The change in the muscle tension was simultaneously recorded in the same preparation. Aconitine (0.1 mu M) increased electrically evoked H-3-ACh release, while at higher con centrations (0.3-3 mu M) it decreased the evoked release and muscle te nsion. High concentrations of aconitine (3-30 mu M) caused a concentra tion-dependent increase in spontaneous H-3-ACh release. All these effe cts were suppressed by tetrodotoxin. The aconitine-induced spontaneous release consisted of two different components: a Ca2+-dependent phasi c release that was inactivated within a few minutes and a Ca2+-indepen dent, long lasting release at a low level. The depression of the Ca2+- dependent quantal release seems attributable to the decline of Ca2+ in flux into the nerve rather than inactivation of sodium channels. We co nclude that aconitine increases and then decreases electrical stimulat ion-evoked ACh release from the motor nerve through prolonged activati on of sodium channels. Further activation of the channels enhances spo ntaneous release and the subsequent complete inactivation of the quant al release may be due to block of Ca2+ influx.