A₂ adenosine receptors inhibit calcium influx through L-type calcium channels in rod photoreceptors of the salamander retina

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 of L-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, (N⁶- [2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine) (DPMA), but not the A₁- or A₃-selective agonists, (R)-N⁶-(1-methyl-2-phenylethyl)adenosine and N⁶-2-(4-aminophenyl)ethyladenosine, also inhibited I_Ca and depolarization-induced [Ca²⁺]i increases. 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 A₂ receptors stimulates PKA to inhibit L-type Ca²⁺ channels in rods resulting in a decreased Ca²⁺ influx that should suppress glutamate release.