Kinetics and subunit composition of NMDA receptors in respiratory‐related neurons

• Published in: Journal of neurochemistry 2005-05, Vol.93 (4), p.812-824
• Main Authors: Paarmann, I., Frermann, D., Keller, B. U., Villmann, C., Breitinger, H. G., Hollmann, M.
• Format: Article
• Language: English
• Subjects: 6-Cyano-7-nitroquinoxaline-2,3-dione - pharmacology; Aminoacid receptors (glycine, glutamate, gaba); Animals; Animals, Newborn; Biological and medical sciences; Blotting, Northern - methods; Brain Stem - cytology; Brain Stem - metabolism; Cell receptors; Cell structures and functions; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Electric Stimulation - methods; Excitatory Amino Acid Agonists - pharmacology; Excitatory Amino Acid Antagonists - pharmacology; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - radiation effects; Fundamental and applied biological sciences. Psychology; hypoglossal nucleus; In Vitro Techniques; Membrane Potentials - drug effects; Membrane Potentials - physiology; Membrane Potentials - radiation effects; Molecular and cellular biology; N-Methylaspartate - pharmacology; Neurons - drug effects; Neurons - physiology; nucleus tractus solitarius; N‐methyl‐d‐aspartate receptor kinetics; Patch-Clamp Techniques - methods; pre‐Bötzinger complex; Protein Subunits - classification; Protein Subunits - genetics; Protein Subunits - metabolism; rat; Rats; Receptors, N-Methyl-D-Aspartate - classification; Receptors, N-Methyl-D-Aspartate - genetics; Receptors, N-Methyl-D-Aspartate - metabolism; Respiration; Restraint, Physical - methods; Reverse Transcriptase Polymerase Chain Reaction - methods; reverse transcription–polymerase chain reaction; RNA, Messenger - biosynthesis; Valine - analogs & derivatives; Valine - pharmacology; Vertebrates: nervous system and sense organs
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2005.03027.x

NMDA receptors are involved in a variety of brainstem functions. The excitatory postsynaptic NMDA currents of pre‐Bötzinger complex interneurons and hypoglossal motoneurons, which are located in the medulla oblongata, show remarkably fast deactivation kinetics of approximately 30 ms compared with NMDA receptors in other types of neurons. Because structural heterogeneity might be the basis for physiological properties, we examined the expression of six NMDA receptor subunits (NMDAR1, NR2A−2D, and NR3A) plus eight NMDR1 splice variants in pre‐Bötzinger complex, hypoglossal and, for comparison, neurons from the nucleus of the solitary tract in young rats using single cell multiplex RT–PCR. Expression of NR2A, NR2B, and NR2D was observed in all three cell types while NR3A was much more abundant in pre‐Bötzinger complex interneurons, which belong to the rhythm generator of respiratory activity. In hypoglossal neurons, the NMDAR1 splice variants NMDAR1–4a and NMDAR1–4b were found. In neurons of the nucleus of the solitary tract, instead of NMDAR1–4b, the NMDAR1–2a splice variant was detected. This differential expression of modulatory splice variants might be the molecular basis for the characteristic functional properties of NMDA receptors, as neurons expressing a special NMDAR1 splice variant at the mRNA level show fast kinetics compared with neurons lacking this splice variant.