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

alpha(2)-Adrenoceptors inhibit Ca2+ influx through voltage-gated Ca2+ channels throughout the nervous system and Ca2+ channel function is modulated following activation of some G-protein coupled receptors. We studied the specific Ca2+ channel inhibited following alpha(2)-adrenoceptor activation in guinea-pig small intestinal myenteric neurons. Ca2+ currents (I-Ca(2+)) were studied using whole-cell patch-clamp techniques. Changes in intracellular Ca2+ (Delta[Ca2+](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 alpha(2)-adrenoceptor agonist, UK 14 304 (0.01-1 mu mol L-1) inhibited I-Ca(2+) and Delta[Ca2+](i); maximum inhibition of I-Ca(2+) was 40%. UK 14 304 did not affect I-Ca(2+) in the presence of SNX-482 or NiCl2 (R-type Ca2+ channel antagonists). UK 14 304 inhibited I-Ca(2+) in the presence of nifedipine, omega-agatoxin IVA or omega-conotoxin, inhibitors of L-, P/Q- and N-type Ca2+ channels. UK 14 304 induced inhibition of I-Ca(2+) was blocked by pertussis toxin pretreatment (1 mu g mL(-1) for 2 h). alpha(2)-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.