We investigated the effects of a GABA(B) agonist baclofen, and serotonin, on the high voltage-activated Ca channel (HVACC) currents in trigeminal motoneurons. Immunohistochemical and reverse transcription-polymerization chain reaction (RT-PCR) studies demonstrated the expression of alpha(1c), alpha(1B), alpha(1A), and alpha(1E) subunits in the trigeminal motoneurons, which form L-, N-, P/Q-, and R-type Ca channels, respectively. By use of specific Ca blockers, it was found that N-type (38'/0), P/Q-type (27%), L-type (16%), and R-type Ca currents (19%) contribute to HVACC I-Ba. Baclofen inhibited HVACC I-Ba in the majority of trigeminal motoneurons tested (n = 15 out of 16), whereas serotonin only did in a small population (n = 5 out of 18). The I-Ba inhibition by baclofen and serotonin was associated with slowing of activation kinetics, relieved by strong prepulse, and prevented by N-ethylmaleimide (NEM), indicative of mediation of Gi/Go. These data provide evidence that GABAergic and serotonergic inputs to trigeminal motoneurons regulate neuronal activities through the inhibition of HVACC currents. (C) 2003 Elsevier Inc. All rights reserved.