Back to Search
Start Over
AMPA receptor current density, not desensitization, predicts selective motoneuron vulnerability.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2000 Oct 01; Vol. 20 (19), pp. 7158-66. - Publication Year :
- 2000
-
Abstract
- Spinal motoneurons are more susceptible to AMPA receptor-mediated injury than are other spinal neurons, a property that has been implicated in their selective degeneration in amyotrophic lateral sclerosis (ALS). The aim of this study was to determine whether this difference in vulnerability between motoneurons and other spinal neurons can be attributed to a difference in AMPA receptor desensitization and/or to a difference in density of functional AMPA receptors. Spinal motoneurons and dorsal horn neurons were isolated from embryonic rats and cultured on spinal astrocytes. Single-cell RT-PCR quantification of the relative abundance of the flip and flop isoforms of the AMPA receptor subunits, which are known to affect receptor desensitization, did not reveal any difference between the two cell populations. Examination of AMPA receptor desensitization by patch-clamp electrophysiological measurements on nucleated and outside-out patches and in the whole-cell mode also yielded similar results for the two cell groups. However, AMPA receptor current density was two- to threefold higher in motoneurons than in dorsal horn neurons, suggesting a higher density of functional AMPA receptors in motoneuron membranes. Pharmacological reduction of AMPA receptor current density in motoneurons to the level found in dorsal horn neurons eliminated selective motoneuron vulnerability to AMPA receptor activation. These results suggest that the greater AMPA receptor current density of spinal motoneurons may be sufficient to account for their selective vulnerability to AMPA receptor agonists in vitro.
- Subjects :
- Animals
Astrocytes cytology
Benzodiazepines pharmacology
Benzothiadiazines pharmacology
Cells, Cultured
Coculture Techniques
Dose-Response Relationship, Drug
Excitatory Amino Acid Antagonists pharmacology
Glutamic Acid metabolism
Glutamic Acid pharmacology
Kainic Acid metabolism
Kainic Acid pharmacology
Membrane Potentials drug effects
Motor Neurons cytology
Motor Neurons drug effects
Patch-Clamp Techniques
Posterior Horn Cells cytology
Posterior Horn Cells drug effects
Posterior Horn Cells metabolism
Protein Isoforms metabolism
RNA, Messenger biosynthesis
Rats
Rats, Sprague-Dawley
Receptors, AMPA analysis
Receptors, AMPA genetics
Reverse Transcriptase Polymerase Chain Reaction
Spinal Cord cytology
Spinal Cord drug effects
Spinal Cord metabolism
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid metabolism
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid pharmacology
Motor Neurons metabolism
Receptors, AMPA metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 20
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 11007871