GABAergic and serotonergic modulation of calcium currents in rat trigeminal motoneurons Seog Bae Oh, a,1 Zheng Gen Piao, a,1 Sang Sup Shin, a Dongjun Ren, b Kyungpyo Park, a and Joong Soo Kim a, * a Department of Physiology, College of Dentistry and Dental Research Institute, Seoul National University, 28-2 Yeongeon-Dong ChongNo-Ku Seoul 110-749, South Korea b Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, 303 E. Chicago Ave., Chicago, IL 60611, USA Received 8 July 2003 Abstract 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 a 1C , a 1B , a 1A , and a 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%), 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 ¼ 15 out of 16), whereas serotonin only did in a small population (n ¼ 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. Ó 2003 Elsevier Inc. All rights reserved. Keywords: Trigeminal motoneurons; High voltage-activated calcium channels; Reverse transcription-polymerization chain reaction; Serotonin; GABA Calcium channels are of great importance in a wide variety of physiological functions including neuro- transmitter release and neuronal excitability in the ner- vous system [1,2]. Neuronal Ca 2þ channels have been classified on the basis of their electrophysiological properties into high voltage-activated Ca channels (HVACC), a class that includes L, N, P/Q-, and R-type, and low voltage-activated Ca channels (LVACC) or T- type Ca channels [3]. Recent advances in molecular bi- ological approaches have elucidated that the subtypes of Ca channels result from expression of different pore- forming a 1A subunits. From these works, it was found that a 1A forms P/Q-type channel, a 1A N-type channel, and both a 1C and a 1D L-type, a 1G , a 1H , and a 1I T-type Ca channels, respectively [3]. However, it is still con- troversial if a 1E forms R-type channels in neurons [4,5]. The trigeminal motor nucleus contains motoneurons, the final output neurons of the brainstem responsible for orofacial motor function such as chewing, feeding, sucking, and speech. To date, most studies on these neurons were focused on characterization of their spontaneous discharge pattern or changes of discharge pattern in response to pharmacological or electrical stimulation onto other brain area or sensory receptors using intracellular or extracellular recording technique [6,7]. However, the ionic mechanisms controlling the motor behavior of trigeminal motoneurons are not un- derstood completely [8–12]. In motor neurons, Ca channels are clearly involved in the release of transmitter from the axon at the neuromuscular junction (NMJ) [13,14], and Ca channels expressed in the soma and dendrites are involved in the control of firing properties Biochemical and Biophysical Research Communications 309 (2003) 58–65 www.elsevier.com/locate/ybbrc BBRC * Corresponding author. Fax: +82-2-762-5107. E-mail address: odolbae@snu.ac.kr (J.S. Kim). 1 These authors contributed equally to this work. 0006-291X/$ - see front matter Ó 2003 Elsevier Inc. All rights reserved. doi:10.1016/S0006-291X(03)01527-4