Synaptic transmission in low extracellular calcium is preserved by 3,4-diaminopyridine

Synaptic transmission in the isolated bullfrog sympathetic ganglion was studied during graded reductions in extracellular Ca++, from the normal of 1.8 mM, in the absence and in the presence of different concentrations of 3,4-diaminopyridine (3,4-DAP). In drug-free Ringer's synaptic transmission, measured as the amplitude of the postganglionic compound action potential, failed progressively as Ca++ was reduced from 1.8 to 0.47 mM. This Ca++-dependence curve of synaptic transmission was shifted to the left (lower Ca++) by 3,4-DAP in dose-related fashion with threshold at 0.1 microM and maximum shift at 10 microM 3,4-DAP. At maximum shift (4- to 5-fold) in the Ca++-dependence curve, compound action potential amplitude was normal at 0.33 mM Ca++ then failed progressively as Ca++ was reduced to 0.12 mM. Also 3,4-DAP causes stimulus-bound repetitive postganglionic responses (SBR) to single preganglionic stimuli (Apatoff and Riker, 1982). SBR were selectively abolished as Ca++ was reduced form 1.8 to 0.47 mM. The data reveal that 3,4-DAP facilitates presynaptic influx or binding of Ca++. Furthermore, the high Ca++ requirement for 3,4-DAP-induced SBR, as well as the difference between threshold drug concentrations for preserving transmission (0.1 microM) and for generating SBR (2-5 microM), lead to the speculation that there may be two presynaptic receptors for 3,4-DAP.