A₁ adenosine receptors inhibit multiple voltage-gated Ca²⁺ channel subtypes in acutely isolated rat basolateral amygdala neurons

1. The anticonvulsant properties of 2-chloroadenosine (CADO) in the basolateral amygdala rely on the activation of adenosine-specific heptahelical receptors. We have utilized whole-cell voltage-clamp electrophysiology to examine the modulatory effects of CADO and other adenosine receptor agonists on voltage-gated calcium channels in dissociated basolateral amygdala neurons. 2. CADO, adenosine, and the A₁ subtype-selective agonists N6-(L-2-Phenylisopropyl)adenosine (R-PIA) and 2-chloro-N⁶-cyclopentyladenosine (CCPA) reversibly modulated whole cell Ba²⁺ currents in a concentration-dependent fashion. CADO inhibition of barium currents was also sensitive to the A₁ antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). 3. The A_2A-selective agonist 4-[2-[[6-Amino-9-(N-ethyl-β-D-ribofuranuronamidosyl)-9H-purin-2-yl] amino]ethyl]benzenepropanoic acid (CGS21680) was without effect. 4. CADO inhibition was predominantly voltage-dependent and sensitive to the sulphydryl-modifying reagent N-ethylmaleimide, implicating a membrane-delimited. G_i/o-coupled signal transduction pathway in the channel regulation. 5. Using Ca²⁺ channel subtype-selective antagonists. CADO inhibition appeared to target multiple channel subtypes, with the inhibition of ω-conotoxin GVIA-sensitive calcium channels being more prominent. 6. Our results indicate that the anti-convulsant effects CADO in the basolateral amygdala may be mediated, in part, by the A₁ receptor-dependent inhibition of voltage gated calcium channels.