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L‐type calcium channels in sympathetic α 3 β 2‐n AC h R ‐mediated cerebral nitrergic neurogenic vasodilation
Author(s) -
Wu C. Y.C.,
Lee R. H.C.,
Chen P.Y.,
Tsai A. P.Y.,
Chen M.F.,
Kuo J.S.,
Lee T. J.F.
Publication year - 2014
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12315
Subject(s) - nicardipine , nicotine , vasodilation , calcium channel blocker , medicine , endocrinology , voltage dependent calcium channel , cerebral arteries , calcium , channel blocker , stimulation , calcium channel , acetylcholine , chemistry , basilar artery , anesthesia
Aim Nicotine stimulation of α 3 β 2‐nicotinic acetylcholine receptors ( α 3 β 2‐n AC hRs) located on sympathetic nerves innervating basilar arteries causes calcium‐dependent noradrenaline release, leading to activation of parasympathetic nitrergic nerves and dilation of basilar arteries. This study aimed to investigate the major subtype of calcium channels located on cerebral peri‐vascular sympathetic nerves, which is involved in nicotine‐induced α 3 β 2‐n AC hR‐mediated nitrergic vasodilation in basilar arteries. Methods Nicotine‐ and transmural nerve stimulation ( TNS )‐induced dilation of isolated porcine basilar arteries was examined using in vitro tissue bath. Nicotine‐induced calcium influx, nicotine‐induced noradrenaline release and nicotine‐induced inward currents were evaluated in rat superior cervical ganglion ( SCG ) neurones, peri‐vascular sympathetic nerves of porcine basilar arteries and α 3 β 2‐n AC h R s‐expressing oocytes respectively. m RNA and protein expression of Ca v 1.2 and Ca v 1.3 channels were detected by RT ‐ PCR , Western blotting and immunohistochemistry. Results Nicotine‐induced vasodilation was not affected by ω ‐ agatoxin TK (selective P/Q‐type calcium channel blocker) or ω ‐conotoxin GVIA (N‐type calcium channel blocker). The vasodilation, however, was inhibited by nicardipine (L‐type calcium channel blocker) in concentrations which did not affect TNS ‐induced vasodilation, suggesting the specific blockade. Nicardipine concentration‐dependently inhibited nicotine‐induced calcium influx in rat SCG neurones and reduced nicotine‐induced noradrenaline release from peri‐vascular sympathetic nerves of porcine basilar arteries. Nicardipine (10 μ m ), which significantly blocked nicotine‐induced vasorelaxation by 70%, did not appreciably affect nicotine‐induced inward currents in α 3 β 2‐n AC hRs‐expressing oocytes. Furthermore, the m RNA s and proteins of Ca v 1.2 and Ca v 1.3 channels were expressed in porcine SCG and peri‐vascular nerve terminals. Conclusion The sympathetic neuronal calcium influx through L‐type calcium channels is modulated by α 3 β 2‐n AC hRs. This calcium influx causes noradrenaline release, initiating sympathetic–parasympathetic (axo‐axonal) interaction‐induced nitrergic dilation of porcine basilar arteries.