Presynaptic action of trifluoperazine at the frog neuromuscular junction

Treatment of frog neuromuscular preparations bathed in basic frog saline (1.8 mM Ca2+) with trifluoperazine (25 microM) caused an increase in MEPP frequency in 6 out of 10 preparations tested. The mean normalised MEPP frequency after 15 min of treatment was approximately 1.5. 10 microM trifluoperazine had a similar effect. In salines containing low concentrations of Ca2+ (50 microM Ca2+, 2 mM Mg2+ or 0 Ca2+, 1 mM EGTA) the stimulatory action of trifluoperazine was more marked and occurred in a higher proportion of the preparations tested (11 out of 14). When evoked release of transmitter was reduced to very low levels by Mg2+-containing salines treatment with trifluoperazine (2.5-25 microM) caused an increase in quantal content of 20-60%. Depolarisation of preparations bathed in standard frog saline by increasing [K+]o to 10 mM resulted in a 10-fold increase in MEPP frequency. This response was inhibited by about 25% in 10 microM trifluoperazine and by about 45% in 25 microM trifluoperazine. Pre-treatment of preparations with trifluoperazine (25 microM) caused a marked reduction in the response of MEPP frequency to tetanic stimulation (50 Hz) both in the presence of an inward electrochemical gradient for Ca2+ (50 microM Ca2+, 2 mM Mg2+) and in a Ca2+-free saline (0 Ca2+, 1 mM EGTA). The effects of trifluoperazine on tetanic enhancement of MEPP frequency are compared to those of other agents and it is shown that the results are inconsistent with an effect of the drug on Ca2+-fluxes at the plasma membrane. It is concluded that trifluoperazine has both stimulatory and inhibitory effects on transmitter release at the frog neuromuscular junction and that the inhibitory effect is probably due to inhibition of excitation-secretion coupling at a point subsequent to Ca2+ mobilization.