title: Modulation of N-type Ca²⁺ currents by moxonidine via imidazoline I₁ receptor activation in rat superior cervical ganglion neurons.
abstract: Moxonidine, an imidazoline deriviatives, suppress the vasopressor sympathetic outflow to produce hypotension. This effect has been known to be mediated in part by suppressing sympathetic outflow via acting imidazoline I(1) receptors (IR(1)) at postganglionic sympathetic neurons. But, the cellular mechanism of IR(1)-induced inhibition of noradrenaline (NA) release is still unknown. We therefore, investigated the effect of IR(1) activation on voltage-dependent Ca(2+) channels which is known to play an pivotal role in regulating NA in rat superior cervical ganglion (SCG) neurons, using the conventional whole-cell patch-clamp method. In the presence of rauwolscine (3 μΜ), which blocks α(2)-adrenoceptor (R(α2)), moxonidine inhibited voltage-dependent Ca(2+) current (I(Ca)) by about 30%. This moxonidine-induced inhibition was almost completely prevented by efaroxan (10 μΜ) which blocks IR(1) as well as R(α2). In addition, ω-conotoxin (CgTx) GVIA (1 μΜ) occluded moxonidine-induced inhibition of I(Ca), but, moxonidine-induced I(Ca) inhibition was not affected by pertussis toxin (PTX) nor shows any characteristics of voltage-dependent inhibition. These data suggest that moxonidine inhibit voltage-dependent N-type Ca(2+) current (I(Ca-N)) via activating IR(1). Finally, moxonidine significantly decreased the frequency of AP firing in a partially reversible manner. This inhibition of AP firing was almost completely occluded in the presence of ω-CgTx. Taken together, our results suggest that activation of IR(1) in SCG neurons reduced I(Ca-N) in a PTX-and voltage-insensitive pathway, and this inhibition attenuated repetitive AP firing in SCG neurons.
authors.affiliation: Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Young-Hwan
authors.initials: YH
authors.lastname: Kim
authors.forename: Taick-Sang
authors.initials: TS
authors.lastname: Nam
authors.forename: Duck-Sun
authors.initials: DS
authors.lastname: Ahn
authors.forename: Seungsoo
authors.initials: S
authors.lastname: Chung
mesh_terms: D000818:Animals; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology*; D054755:Imidazoline Receptors / Q000819:agonists*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D020864:Calcium Channels, N-Type; D007093:Imidazoles; D054755:Imidazoline Receptors; D014665:Vasodilator Agents; C410887:imidazoline I1 receptors; C043482:moxonidine; D009638:Norepinephrine