Reduced NR2A expression and prolonged decay of NMDA receptor-mediated synaptic current in rat vagal motoneurons following axotomy.
To elucidate characteristic changes in the N-methyl-D-aspartate (NMDA) receptor on neurons following axotomy, subunit expressions and functional features of the NMDA receptor were examined in the dorsal motor nucleus of vagus (DMV) of rats receiving vagal axotomy at the neck. Western blotting analysis demonstrated that the expression of NR2A decreased 2-3 days after in vivo axotomy, while expression of NR1 and NR2B, NR2C and NR2D subunits did not change significantly. To examine the functional changes, patch clamp recordings in whole-cell mode were employed on the axotomized DMV neurons identified by retrograde labelling with fluorescent dye. The amplitude ratios of ifenprodil-sensitive components of NMDA response and D,L-2-amino-5-phosphovaleric acid (APV)-sensitive evoked postsynaptic current increased after axotomy. In addition, APV-sensitive postsynaptic currents exhibited a longer decay time in identified axotomized vagal motoneurons than in control neurons. No significant differences in the current density of the NMDA response and the peak amplitude of APV-sensitive synaptic currents were observed between axotomized and intact DMV neurons. In conclusion, a decrease in NR2A expression results in the appearance of functional characteristics of the NMDA receptor predominantly containing the NR2B subunit. This might lead to a long-term increase of the susceptibility of neurons to excitotoxicity.
Nabekura
Junichi
J
Department of Cellular and System Physiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka 812-8582, Japan. nabekura@physiol2.med.kyushu-u.ac.jp
Ueno
Tsuyoshi
T
Katsurabayashi
Shutaro
S
Furuta
Akiko
A
Akaike
Norio
N
Okada
Masayoshi
M
D000818:Animals; D019771:Axotomy; D009046:Motor Neurons / Q000502:physiology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D013997:Time Factors; D014630:Vagus Nerve / Q000166:cytology / Q000502:physiology*
C120997:NR2A NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate