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Experimental Physiology – Research Paper : Modulation of N‐type calcium currents by presynaptic imidazoline receptor activation in rat superior cervical ganglion neurons
Author(s) -
Chung Seungsoo,
Ahn DuckSun,
Kim YoungHwan,
Kim YoonSuk,
Joeng JiHyun,
Nam TaickSang
Publication year - 2010
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2010.053355
Subject(s) - imidazoline receptor , superior cervical ganglion , calcium , neuroscience , ganglion , biology , chemistry , endocrinology , medicine
Presynaptic imidazoline receptors (R i‐pre ) are found in the sympathetic axon terminals of animal and human cardiovascular systems, and they regulate blood pressure by modulating the release of peripheral noradrenaline (NA). The cellular mechanism of R i‐pre ‐induced inhibition of NA release is unknown. We, therefore, investigated the effect of R i‐pre activation on voltage‐dependent Ca 2+ channels in rat superior cervical ganglion (SCG) neurons, using the conventional whole‐cell patch‐clamp method. Cirazoline (30 μ m ), an R i‐pre agonist as well as an α‐adrenoceptor (R α ) agonist, decreased Ca 2+ currents ( I Ca ) by about 50% in a voltage‐dependent manner with prepulse facilitation. In the presence of low‐dose rauwolscine (3 μ m ), which blocks the α 2 ‐adrenoceptor (R α2 ), cirazoline still inhibited I Ca by about 30%, but prepulse facilitation was significantly attenuated. This inhibitory action of cirazoline was almost completely prevented by high‐dose rauwolscine (30 μ m ), which blocks R i‐pre as well as R α2 . In addition, pretreatment with LY320135 (10 μ m ), another R i‐pre antagonist, in combination with low‐dose rauwolscine (3 μ m ), also blocked the R α2 ‐resistant effect of cirazoline. Addition of guanosine‐5′‐ O ‐(2‐thiodiphosphate) (2 m m ) to the internal solutions significantly attenuated the action of cirazoline. However, pertussis toxin (500 ng ml −1 ) did not significantly influence the inhibitory effect of cirazoline. Moreover, cirazoline (30 μ m ) suppressed M current in SCG neurons cultured overnight. Finally, ω‐conotoxin (ω‐CgTx) GVIA (1 μ m ) obstructed cirazoline‐induced current inhibition, and cirazoline (30 μ m ) significantly decreased the frequency of action potential firing in a partly reversible manner. This cirazoline‐induced inhibition of action potential firing was almost completely occluded in the presence of ω‐CgTx. Taken together, our results suggest that activation of R i‐pre in SCG neurons reduced N‐type I Ca in a pertussis toxin‐ and voltage‐insensitive pathway, and this inhibition attenuated repetitive action potential firing in SCG neurons.