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Modulation of N-type calcium currents by presynaptic imidazoline receptor activation in rat superior cervical ganglion neurons

 Seungsoo Chung  ;  Duck-Sun Ahn  ;  Young-Hwan Kim  ;  Yoon-Suk Kim  ;  Ji-Hyun Joeng  ;  Taick-Sang Nam 
 EXPERIMENTAL PHYSIOLOGY, Vol.95(10) : 982-993, 2010 
Journal Title
Issue Date
Action Potentials ; Adrenergic alpha-2 Receptor Antagonists/pharmacology ; Animals ; Benzofurans/pharmacology ; Calcium Channel Blockers/pharmacology* ; Calcium Channels, N-Type/drug effects* ; Calcium Channels, N-Type/metabolism ; Calcium Signaling/drug effects* ; Cells, Cultured ; Dose-Response Relationship, Drug ; Guanosine Diphosphate/analogs & derivatives ; Guanosine Diphosphate/pharmacology ; Imidazoles/pharmacology* ; Imidazoline Receptors/agonists* ; Imidazoline Receptors/metabolism ; Kinetics ; Male ; Neurons/drug effects* ; Neurons/metabolism ; Norepinephrine/metabolism ; Patch-Clamp Techniques ; Pertussis Toxin/pharmacology ; Potassium Channels/drug effects ; Potassium Channels/metabolism ; Presynaptic Terminals/drug effects* ; Presynaptic Terminals/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Presynaptic/agonists* ; Receptors, Presynaptic/metabolism ; Superior Cervical Ganglion/cytology ; Superior Cervical Ganglion/drug effects* ; Superior Cervical Ganglion/metabolism ; Thionucleotides/pharmacology ; Yohimbine/pharmacology ; omega-Conotoxin GVIA/pharmacology
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 μM), 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 μM), 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 μM), which blocks R(i-pre) as well as R(α2). In addition, pretreatment with LY320135 (10 μM), another R(i-pre) antagonist, in combination with low-dose rauwolscine (3 μM), also blocked the R(α2)-resistant effect of cirazoline. Addition of guanosine-5-O-(2-thiodiphosphate) (2 mm) 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 μM) suppressed M current in SCG neurons cultured overnight. Finally, omega-conotoxin (omega-CgTx) GVIA (1 μM) obstructed cirazoline-induced current inhibition, and cirazoline (30 μM) 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 omega-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.
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1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Young Hwan(김영환)
Nam, Taick Sang(남택상)
Ahn, Duk Sun(안덕선) ORCID logo https://orcid.org/0000-0001-9351-6951
Chung, Seung Soo(정승수) ORCID logo https://orcid.org/0000-0002-3119-9628
Joeng, Ji Hyun(정지현)
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