EFFECTS OF TETRANDRINE ON SPONTANEOUS AND EVOKED RELEASE OF ACETYLCHOLINE AT THE MOUSE NEUROMUSCULAR-JUNCTION

The action of tetrandrine on spontaneous and phasic acetylcholine (ACh ) release was investigated at the mouse neuromuscular junction recordi ng miniature endplate potentials (MEPPs) and endplate potentials. Supe rfusion of muscles with tetrandrine (10 mu M) in normal Krebs-Ringer s olution induced an increase of the mean regular MEPP amplitude and the overall MEPP frequency. In addition a larger than normal proportion o f high-amplitude MEPPs appeared, described as ''giants.'' This enhance ment by tetrandrine of spontaneous ACh release also occurred in the pr esence of tetrodotoxin (1 mu M). In elevated magnesium Krebs-Ringer so lution the mean amplitude as well as the quantal content of endplate p otentials was reduced simultaneously with the enhancement of spontaneo us ACh release. Superfusion of muscles with emetine (20 mu M), an alka loid chemically of the same kind as tetrandrine, induced an enhancemen t of spontaneous ACh release as recorded by MEPPs qualitatively simila r to that of tetrandrine. These results suggest that the isoquinolines tetrandrine and emetine similarly increased the spontaneous ACh relea se. This action of tetrandrine appeared to be presynaptic and was acco mpanied by a decrease of phasic ACh release.