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 ICa 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.
All Science Journal Classification (ASJC) codes
- Cellular and Molecular Neuroscience