Role of AMPA Receptor Desensitization and the Side Effects of a DMSO Vehicle on Reticulospinal EPSPs and Locomotor Activity
Open Access
- 1 December 2005
- journal article
- research article
- Published by American Physiological Society in Journal of Neurophysiology
- Vol. 94 (6), 3951-3960
- https://doi.org/10.1152/jn.00201.2005
Abstract
Activation of the vertebrate locomotor network is mediated by glutamatergic synaptic drive, normally initiated by the brain stem. Previous investigations have studied the role of glutamate receptors, especially NMDA receptors, in generating and regulating locomotor pattern generation. Few studies, however, have focused on the role of AMPA receptors in shaping network activity, especially with regard to their rapid desensitization. It is important to determine whether AMPA receptor desensitization plays a role in regulating neuronal network activity. We examined this question on both the network and synaptic levels in the lamprey ( Lampetra fluviatilis) spinal cord using a selective and potent inhibitor of AMPA receptor desensitization, cyclothiazide (CTZ). The solvent dimethyl sulfoxide (DMSO) is commonly used to dissolve this drug, as well as many others. Unexpectedly, the vehicle alone already at 0.02%, but not at 0.01%, caused significant increases in excitatory postsynaptic potential (EPSP) amplitudes and NMDA-induced locomotor frequency. The results indicate that DMSO may have a profound influence when used ≥0.02%, a concentration 10–50 times less than that most commonly used. Subsequently we applied CTZ concentrations ≤10 μM (DMSO ≤0.01%). CTZ (1.25–5 μM) caused an appreciable and significant increase in EPSPs mediated by non-NMDA receptors and in both AMPA- and NMDA-induced locomotor frequency, but no effects on EPSPs mediated by NMDA receptors. From the effects of CTZ it is apparent that AMPA receptor desensitization plays an important role in determining locomotor frequency and that this is likely a result of its limiting function on AMPA receptor–mediated EPSPs.Keywords
This publication has 46 references indexed in Scilit:
- The Spinal GABAergic System Is a Strong Modulator of Burst Frequency in the Lamprey Locomotor NetworkJournal of Neurophysiology, 2004
- Identification of a Site in GluR1 and GluR2 That Is Important for Modulation of Deactivation and DesensitizationMolecular Pharmacology, 2003
- Mechanism of glutamate receptor desensitizationNature, 2002
- Desensitization of AMPA Receptors Limits the Amplitude of EPSPs and the Excitability of Motoneurons of the Rat Isolated Spinal CordEuropean Journal of Neuroscience, 1995
- Cyclothiazide Modulates AMPA Receptor‐Mediated Increases in Intracellular Free Ca2+ and Mg2+ in Cultured Neurons from Rat BrainJournal of Neurochemistry, 1995
- Properties of vertebrate glutamate receptors: Calcium mobilization and desensitizationProgress in Neurobiology, 1992
- Dimethyl sulfoxide (DMSO) blocks GABA-induced current in rat dorsal root ganglion neuronsNeuroscience Letters, 1992
- Glutamate receptor desensitization and its role in synaptic transmissionNeuron, 1989
- The fusogenic substance dimethyl sulfoxide enhances exocytosis in motor nerve endingsBiochimica et Biophysica Acta (BBA) - Biomembranes, 1985
- Facilitatory effect of some drugs on transmission in the frog sympathetic ganglionJournal of the Autonomic Nervous System, 1982