NMDA-induced burst discharge in guinea pig trigeminal motoneurons in vitro.
1. The responses of guinea pig trigeminal motoneurons (TMNs) to N-methyl-D,L-aspartate (NMA) were studied using brain stem slice preparations and whole cell patch-clamp (n = 89) or conventional microelectrode (n = 22) recording techniques. The primary goals of this study were to determine whether N-methyl-D-aspartate (NMDA) receptor activation would produce spontaneous bursting activity in TMNs and, if so, the underlying mechanisms responsible for the generation of these bursts. 2. Bath-applied NMA (100-300 microM, n = 80) in standard perfusion medium elicited depolarization, increase in apparent input resistance (Rinp), and rhythmic burst discharges (1-90 s in duration) from TMNs. These effects were blocked by the NMDA receptor antagonist DL-2-amino-5-phosphonopentanoic acid (AP5, 30 microM, n = 6), but not by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 5-10 microM, n = 10). Furthermore, the burst-inducing effect of NMA was not mimicked by the non-NMDA receptor agonists kainate (KA, 5-10 microM, n = 6) and (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA, 5-10 microM, n = 5). 3. In tetrodotoxin (TTX) treatment conditions (n = 13), NMA elicited depolarization, an increase in apparent Rinp, and rhythmic membrane potential oscillations without action potential bursts (i.e., plateau potentials), suggesting that the effects of NMA observed in the TTX-free condition resulted from activation of postsynaptic NMDA receptors. 4. Graded depolarization of neurons (n = 20) by intracellular direct current injection generally led to a graded increase in frequency and duration of the NMA-induced bursts and plateau potentials until these rhythmic events eventually became transformed into continuous spike discharge and maintained depolarization, respectively. Removal of Mg2+ from the perfusion medium (n = 11) also turned the bursts and plateau potentials into continuous spike discharge and maintained depolarization, respectively. 5. The effects of NMA on the current-voltage (I-V) curve after a depolarizing ramp voltage-clamp command (15-20 mV/s) were examined (n = 40). Under NMA (100-300 microM) conditions, the I-V relationship exhibited a region of negative slope conductance (NSC) between -60 and -35 mV, thus making the I-V relationship N-shaped. The NSC was abolished by AP5 (30 microM, n = 8), but not by CNQX (5-10 microM, n = 6). The I-V relationship in AMPA (3-10 microM, n = 5) or KA (3-10 microM, n = 5) was almost linear between -80 and -30 mV.(ABSTRACT TRUNCATED AT 400 WORDS)
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D004594:Electrophysiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008274:Magnesium / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008839:Microelectrodes; D009046:Motor Neurons / Q000187:drug effects*; D016202:N-Methylaspartate / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology; D014276:Trigeminal Nerve / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D018690:Excitatory Amino Acid Agonists; D015221:Potassium Channels; D016194:Receptors, N-Methyl-D-Aspartate; D013779:Tetrodotoxin; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D008274:Magnesium