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 Ca2+ 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 ICa and Ca2+ imaging of synaptic terminals in cones demonstrate that adenosine inhibited both ICa and the depolarization‐evoked Ca2+ increase in cone terminals in a dose‐dependent manner from 1 to 50 μM. 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. © 2007 Wiley‐Liss, Inc.