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 I1 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 (3μΜ), which blocks α2-adrenoceptor (Rα2), moxonidine inhibited voltage-dependent Ca2+ current (ICa) by about 30%. This moxonidine-induced inhibition was almost completely prevented by efaroxan (10μΜ) which blocks IR1 as well as Rα2. In addition, ω-conotoxin (CgTx) GVIA (1μΜ) occluded moxonidine-induced inhibition of ICa, but, moxonidine-induced ICa 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 ω-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.