Trifluoperazine-sensitive activation of the spontaneous transmitter release at the frog motor endplates by low doses of procaine.

Low concentrations of procaine (10(-6)-5 X 10(-5) mol/l) induced a significant increase of the spontaneous quantal transmitter release in the neuromuscular junctions of the frog cutaneous pectoris nerve-muscle preparation. The frequency of miniature endplate potentials (mepps) was increased although their size slightly decreased probably on the account of a partial block of Na+-channels at the postsynaptic membrane. The activatory effect of pre-caine was not altered under experimental conditions known to change the Ca2+ fluxes across the nerve terminal membrane such as using a Ca2+-free Ringer, or a Ca2+-channel blocker (D600), a high K+ Ringer or, finally, a low Na+ Ringer. In the presence of caffeine no change of procaine-induced activation appeared. Trifluoperazine (TFP), in a concentration known to specifically block calmodulin, completely blocked the procaine-induced increase of mepp frequency. These data suggest that procaine presumably by way of a calmodulin-dependent mechanism is related to the free cytosolic Ca2+ equilibrium. It is possible that procaine increases the free cytosolic Ca2+ concentration by blocking an active calmodulin-dependent Ca2+ extrusion mechanism.