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α 2 ‐Adrenoceptors couple to inhibition of R‐type calcium currents in myenteric neurons
Author(s) -
Bian X.,
Galligan J. J.
Publication year - 2007
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.2007.00976.x
Subject(s) - pertussis toxin , myenteric plexus , nifedipine , depolarization , chemistry , patch clamp , voltage dependent calcium channel , agonist , channel blocker , receptor , medicine , endocrinology , biophysics , calcium , g protein , biology , biochemistry , immunohistochemistry
α 2 ‐Adrenoceptors inhibit Ca 2+ influx through voltage‐gated Ca 2+ channels throughout the nervous system and Ca 2+ channel function is modulated following activation of some G‐protein coupled receptors. We studied the specific Ca 2+ channel inhibited following α 2 ‐adrenoceptor activation in guinea‐pig small intestinal myenteric neurons. Ca 2+ currents (I Ca 2+ ) were studied using whole‐cell patch‐clamp techniques. Changes in intracellular Ca 2+ (Δ[Ca 2+ ] i ) in nerve cell bodies and varicosities were studied using digital imaging where Ca 2+ influx was evoked by KCl (60 mmol L −1 ) depolarization. The α 2 ‐adrenoceptor agonist, UK 14 304 (0.01–1 μ mol L −1 ) inhibited I Ca 2+ and Δ[Ca 2+ ] 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 NiCl 2 (R‐type Ca 2+ channel antagonists). UK 14 304 inhibited I Ca 2+ in the presence of nifedipine, ω‐agatoxin IVA or ω‐conotoxin, inhibitors of L‐, P/Q‐ and N‐type Ca 2+ channels. UK 14 304 induced inhibition of I Ca 2+ was blocked by pertussis toxin pretreatment (1 μ g mL −1 for 2 h). α 2 ‐Adrenoceptors couple to inhibition of R‐type Ca 2+ 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.