α2-Adrenoceptors couple to inhibition of R-type calcium currents in myenteric neurons

Abstract

α2-Adrenoceptors inhibit Ca2+ influx through voltage-gated Ca2+ channels throughout the nervous system and Ca 2+ channel function is modulated following activation of some G-protein coupled receptors. We studied the specific Ca2+ channel inhibited following α2-adrenoceptor activation in guinea-pig small intestinal myenteric neurons. Ca2+ currents (I Ca2+) were studied using whole-cell patch-clamp techniques. Changes in intracellular Ca2+ (Δ[Ca 2+]i) in nerve cell bodies and varicosities were studied using digital imaging where Ca2+ influx was evoked by KCl (60 mmol L-1) depolarization. The α2-adrenoceptor agonist, UK 14 304 (0.01-1 μmol L-1) inhibited ICa2+ and Δ[Ca2+]i; maximum inhibition of I Ca2+ was 40%. UK 14 304 did not affect ICa2+ in the presence of SNX-482 or NiCl2 (R-type Ca 2+ channel antagonists). UK 14 304 inhibited ICa2+ in the presence of nifedipine, ω-agatoxin IVA or ω-conotoxin, inhibitors of L-, P/Q- and N-type Ca2+ channels. UK 14 304 induced inhibition of ICa2+ was blocked by pertussis toxin pretreatment (1 μg mL-1 for 2 h). α2-Adrenoceptors couple to inhibition of R-type Ca2+ channels via a pertussis toxin-sensitive pathway in myenteric neurons. R-type channels may be a target for the inhibitory actions of noradrenaline released from sympathetic nerves on to myenteric neurons. © 2007 The Authors.