Adenosine inhibits voltage-dependent Ca²⁺ influx in cone photoreceptor terminals of the tiger salamander retina

Endogenous adenosine has already been shown to inhibit transmitter release from the rod synapse by suppressing Ca²⁺ influx through voltage-gated Ca²⁺ channels. However, it is not clear how adenosine modulates the cone synapse. Cone photoreceptors, like rod photoreceptors, also possess L-type Ca²⁺ channels that regulate the release of L-glutamate. To assess the impact of adenosine on Ca²⁺ influx though voltage-gated Ca ²⁺ channels in cone terminals, whole-cell perforated-patch clamp recording and Ca²⁺ imaging with fluo-4 were used on isolated cones and salamander retinal slices. Synaptic markers (VAMP and piccolo) and activity-dependent dye labeling revealed that tiger salamander cone terminals contain a broad, vesicle-filled cytoplasmic extension at the base of the somatic compartment, which is unlike rod terminals that contain one or more thin axons, each terminating in a large bulbous synaptic terminal. The spatiotemporal Ca²⁺ responses of the cone terminals do not differ significantly from the Ca²⁺ responses of the soma or inner segment like that observed in rods. Whole-cell recording of cone I_Ca and Ca²⁺ imaging of synaptic terminals in cones demonstrate that adenosine inhibited both I _Ca and the depolarization-evoked Ca²⁺ increase in cone terminals in a dose-dependent manner from 1 to 50 μM, with an EC₅₀ of 15.6 nM. These results indicate that, as in rods, adenosine's ability to suppress voltage-dependent Ca²⁺ channels at the cone synapse will limit the amount of L-glutamate released. Therefore, adenosine has an inhibitory effect on L-glutamate release at the first synapse, which likely favors elevated adenosine levels in the dark or during dark-adapted conditions.