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 A2A-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 A1 receptor-dependent inhibition of voltage gated calcium channels.
McCool
B A
BA
Department of Medical Pharmacology and Toxicology, The Texas A&M University System Health Science Center, College Station, Texas, TX 77843, USA. mccool@medicine.tamu.edu
Farroni
J S
JS
D015762:2-Chloroadenosine / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism; D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D005033:Ethylmaleimide / Q000494:pharmacology; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D008297:Male; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D015398:Signal Transduction; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D020867:omega-Agatoxin IVA / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D015220:Calcium Channels; D018047:Receptors, Purinergic P1; D010566:Virulence Factors, Bordetella; D020867:omega-Agatoxin IVA; D015762:2-Chloroadenosine; D020866:omega-Conotoxin GVIA; D000241:Adenosine; D005033:Ethylmaleimide