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A 1 adenosine receptors inhibit multiple voltage‐gated Ca 2+ channel subtypes in acutely isolated rat basolateral amygdala neurons
Author(s) -
McCool Brian A,
Farroni Jeffery S
Publication year - 2001
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703884
Subject(s) - adenosine receptor , adenosine , basolateral amygdala , agonist , chemistry , adenosine a1 receptor , adenosine receptor antagonist , calcium channel , voltage dependent calcium channel , pharmacology , receptor , medicine , biology , biochemistry , calcium , organic chemistry
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 A 1 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 A 1 antagonist 1,3‐dipropyl‐8‐cyclopentylxanthine (DPCPX). 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. 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. Using Ca 2+ 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 A 1 receptor‐dependent inhibition of voltage gated calcium channels.British Journal of Pharmacology (2001) 132 , 879–888; doi: 10.1038/sj.bjp.0703884