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 (IR1) at postganglionic sympathetic neurons. But, the cellular mechanism of IR1-induced inhibition of noradrenaline (NA) release is still unknown. We therefore, investigated the effect of IR1 activation on voltage-dependent Ca2+ 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 mu M), which blocks alpha(2)-adrenoceptor (R-alpha 2), moxonidine inhibited voltage-dependent Ca2+ current (10) by about 30%. This moxonidine-induced inhibition was almost completely prevented by efaroxan (10 mu M) which blocks IR1 as well as R-alpha 2. In addition, omega-conotoxin (CgTx) GVIA (1 mu M) 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 Ca2+ current (ICa-N) via activating IR1. 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 omega-CgTx. Taken together, our results suggest that activation of IR1 in SCG neurons reduced ICa-N in a PTX-and voltage-insensitive pathway, and this inhibition attenuated repetitive AP firing in SCG neurons. (C) 2011 Elsevier Inc. All rights reserved.