Aconitine-Induced Increase and Decrease of Acetylcholine Release in the Mouse Phrenic Nerve-Hemidiaphragm Muscle Preparation

Abstract

ABSTRACT-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 prepara tion. Aconitine (0.1 ttM) increased electrically evoked 3H-ACh release, while at higher concentrations (0.3 3 pM) it decreased the evoked release and muscle tension. High concentrations of aconitine (3 30 pM) caused a concentration-dependent increase in spontaneous 3H-ACh release. All these effects were sup pressed by tetrodotoxin. The aconitine-induced spontaneous release consisted of two different components: a Ca"-dependent phasic release that was inactivated within a few minutes and a Ca" -independent, long lasting release at a low level. The depression of the Ca" -dependent quantal release seems attributable to the decline of Ca" 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 Ca" influx.

Aconitine facilitates spontaneous transmitter release at rat ventromedial hypothalamic neurons

“…The present study also demonstrated that aconitine increases the frequency of both spontaneous GABAergic IPSCs and glutamatergic EPSCs in rat VMH neurons. Comparable neurotransmitter release response have been described for the spontaneous acetylcholine release in the mouse (Okazaki et al ., 1994) and rat (Onur et al ., 1995) neuromuscular junctions. Since the mean amplitude of spontaneous IPSCs was not significantly changed (Figure 2), aconitine does not appear to alter the sensitivity of postsynaptic GABA A ‐receptor‐channel complexes to transmitter released from presynaptic nerve terminals.…”

Calcium antagonists cause dry mouth by inhibiting resting saliva secretion

“…To investigate the effect of cell depolarization on the CCh (10 μM)-induced [Ca 2+ ]i elevation, the Na + channel openers, veratridine (Son et al, 2004) and aconitine (Okazaki et al, 1994), were applied with 10 μM CCh and the effects were compared with those of 10 μM CCh alone. Veratridine (10 μM) and aconitine (10 μM) significantly augmented the CCh (10 μM)-induced [Ca 2+ ]i elevation (Fig.…”

“…Since the Na + channels openers result in depolarization of the plasma membrane by inducing Na + invasion (Son et al, 2004;Okazaki et al, 1994), the finding that both the drugs augmented the CCh (10 μM)-induced [Ca 2+ ]i elevation indicated that membrane depolarization caused the Ca 2+ influx by activating the voltage-dependent Ca 2+ channels (Fig. 2).…”