Modulation of high-threshold transmission between heart interneurons of the medicinal leech by FMRF-NH2

1. We examined high-threshold synaptic transmission between oscillatory pairs of leech heart interneurons. Inhibitory postsynaptic currents (IPSCs) could be reliably evoked by depolarizing the presynaptic neuron in voltage clamp from a holding potential of -35 mV. At this presynaptic potential, the Ca2+ currents underlying graded transmission are completely inactivated, and we conclude that a high-threshold Ca2+ current is extant in heart interneurons. Further evidence for this was that inhibitory postsynaptic currents were blocked when Co2+ replaced Ca2+ in the saline and thus high-threshold transmission was dependent on the presence of external Ca2+. 2. When IPSCs were evoked by a 200-ms duration voltage step from a holding potential of -35 mV in the presynaptic neuron, the time course of turn-on of the IPSC consisted of a fast (time-to-peak = 17.5 +/- 1.93 (SE) ms [n = 7]) and a slow (time-to-peak = 250 +/- 28.5 ms [n = 8]) component. FMRF-NH2 reduced the amplitude of the fast component but did not affect the slow component. When the presynaptic voltage step was ended the IPSC turned off with a single exponential time course. FMRF-NH2 slowed the time course of turn-off of the IPSC. 3. When IPSCs were evoked by a 1500-ms duration voltage step from a holding potential of -35 mV in the presynaptic neuron, these IPSCs peaked around 300 ms. Following the peak, the IPSC decayed with a single exponential time course. FMRF-NH2 accelerated the time course of this decay. At potentials of 0 mV and +5 mV, FMRF-NH2 produced a significant decrease in the peak current and at potentials of -5 mV and 0 mV, produced a significant decrease in the current integral. 4. High-threshold IPSCs could also be evoked by a spike in the presynaptic neuron. Bath application of 1 microM FMRF-NH2 decreased the amplitude of the spike-evoked IPSC and slowed the time course of its falling phase. 5. We examined the effect of FMRF-NH2 on the quantal synaptic transmission. Bath-application of FMRF-NH2 increased binomial p, the probability of release, and decreased binomial n, the number of units available for release. FMRF-NH2 had no effect on q, the unit size, when calculated from the distributions of PSPs, and increased the coefficient of variation (CV). 6. The lack of a change in q and the increase in CV suggested that FMRF-NH2 acted at a presynaptic location.(ABSTRACT TRUNCATED AT 400 WORDS)