A2 Adenosine Receptors Inhibit Calcium Influx Through L-Type Calcium Channels in Rod Photoreceptors of the Salamander Retina

Abstract

Presynaptic inhibition is a major mechanism for regulating synaptic transmission in the CNS and adenosine inhibits Ca2+ currents ( I Ca) to reduce transmitter release at several synapses. Rod photoreceptors possess L-type Ca2+ channels that regulate the release ofl-glutamate. In the retina, adenosine is released in the dark when l-glutamate release is maximal. We tested whether adenosine inhibits I Ca and intracellular Ca2+ increases in rod photoreceptors in retinal slice and isolated cell preparations. Adenosine inhibited both I Ca and the [Ca2+]i increase evoked by depolarization in a dose-dependent manner with ∼25% inhibition at 50 μM. An A2-selective agonist, ( N 6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine) (DPMA), but not the A1- or A3-selective agonists, ( R)- N 6-(1-methyl-2-phenylethyl)adenosine and N 6-2-(4-aminophenyl)ethyladenosine, also inhibited I Ca and depolarization-induced [Ca2+]iincreases. An inhibitor of protein kinase A (PKA), Rp-cAMPS, blocked the effects of DPMA on both I Ca and the depolarization-evoked [Ca2+]i increase in rods. The results suggest that activation of A2receptors stimulates PKA to inhibit L-type Ca2+channels in rods resulting in a decreased Ca2+influx that should suppress glutamate release.