In leeches, two pairs of reciprocally inhibitory heart interneurons that form the core oscillators of the pattern-generating network for heartbeat possess both high- and low-threshold (HVA and LVA) Ca channels. LVA Ca current has two kinetically distinct components (one rapidly activating/inactivating, I_CaF, and another slowly activating/inactivating, I_CaS) that mediate graded transmission, generate plateau potentials driving burst formation, and modulate spike-mediated transmission between heart interneurons. Here we used different stimulating protocols and inorganic Ca channel blockers to separate the effects of I_CaF and I_CaS on graded synaptic transmission and determine their interaction and relative efficacy. Ca²⁺ entering via I_CaF channels is more efficacious in mediating release than that entering via I_CaS channels. The rate of Ca²⁺ entry via LVA Ca channels appears to be as critical as the amount of delivered Ca²⁺ for synaptic transmission. LVA Ca currents and associated graded transmission were selectively blocked by 1 mM Ni²⁺ leaving spike-mediated transmission unaffected. Nevertheless, 1 mM Ni²⁺ affected homosynaptic enhancement of spike-mediated transmission that depends on background Ca²⁺ provided by LVA Ca channels. Ca²⁺ provided by both I_CaF and I_CaS depletes a common pool of readily releasable synaptic vesicles. The balance between availability of vesicles, and Ca²⁺ concentration and its time course determine the strength of inhibitory transmission between heart interneurons. We argue that Ca²⁺ from multichannel domains arising from I_CaF channels, clustered near but not directly associated with the release trigger, and Ca²⁺ radially diffusing from generally distributed I_CaS channels interact at common release sites to mediate graded transmission.