| Abstrakt: |
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.CADO, adenosine, and the A1subtype‐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 A1antagonist 1,3‐dipropyl‐8‐cyclopentylxanthine (DPCPX).The A2A‐selective agonist 4‐[2‐[[6‐Amino‐9‐(N‐ethyl‐β‐D‐ribofuranuronamidosyl)‐9H‐purin‐2‐yl]amino]ethyl]benzenepropanoic acid (CGS21680) was without effect.CADO inhibition was predominantly voltage‐dependent and sensitive to the sulphydryl‐modifying reagent N‐ethylmaleimide, implicating a membrane‐delimited, Gi/o‐coupled signal transduction pathway in the channel regulation.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.Our results indicate that the anti‐convulsant effects CADO in the basolateral amygdala may be mediated, in part, by the A1receptor‐dependent inhibition of voltage gated calcium channels. |
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