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 A(l) subtype-selective agonists N6-(L-2-Phenylisopropyl)adenosine (R-PIA) and 2-chloro-N-6-cyclopentyladenosine (CCPA) reversibly modulated whole cell Ba-2 currents in a concentration-dependent fashion. CADO inhibition of barium currents was also sensitive to the Al antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). 3 The A(2A)-selective agonist 4-[2-[[6-Amino-9-(N-ethyl-beta -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 omega -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 Al receptor-dependent inhibition of voltage gated calcium channels.