Modulation of N-type calcium currents by presynaptic imidazoline receptor activation in rat superior cervical ganglion neurons.
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.
Chung
Seungsoo
S
Brain Korea 21 Project for Medical Science, Seoul, Republic of Korea.
Ahn
Duck-Sun
DS
Kim
Young-Hwan
YH
Kim
Yoon-Suk
YS
Joeng
Ji-Hyun
JH
Nam
Taick-Sang
TS
D000200:Action Potentials; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020864:Calcium Channels, N-Type / Q000187:drug effects* / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D054755:Imidazoline Receptors / Q000819:agonists* / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017661:Receptors, Presynaptic / Q000819:agonists* / Q000378:metabolism; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013873:Thionucleotides / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D058669:Adrenergic alpha-2 Receptor Antagonists; D001572:Benzofurans; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D007093:Imidazoles; D054755:Imidazoline Receptors; D015221:Potassium Channels; D017661:Receptors, Presynaptic; D013873:Thionucleotides; D006153:Guanosine Diphosphate; D015016:Yohimbine; C023427:guanosine 5'-O-(2-thiodiphosphate); D020866:omega-Conotoxin GVIA; C110158:LY 320135; D037342:Pertussis Toxin; C014282:cirazoline; D009638:Norepinephrine