Effects of methylprednisolone on the GABA- and glutamate-induced currents: relevance to glucocorticoid-induced neurotoxicity and brain aging.
We have previously shown that both epidural administration and microinjection of methylprednisolone (MP) produces neuronal hyperexcitability in the murine spinal cord in vivo. In this study, the whole-cell patch-clamp technique was used to describe and characterize MP-induced neuronal hyperexcitability. Exposure of 10- to 18-day old dissociated spinal cord cultures to 65 microM-8 mM MP caused a concentration-dependent increase in the firing rate. MP (1 mM) increased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and spontaneous inhibitory postsynaptic currents (sIPSCs). The amplitude of the sEPSCs was also increased in response to 1 mM MP, whereas sIPSCs became smaller in size in the presence of MP. MP (1 mM) reduced the amplitude of the gamma-aminobutyric acid (GABA)-induced currents, whereas it increased the amplitude of the glutamate-induced currents. And finally; MP (1 mM), by itself, did not change the overall postsynaptic membrane conductance. These observations suggest that (1) MP can act as an excitatory agent in vitro, (2) it can act at the presynaptic as well as the postsynaptic level, and (3) it affects spinal cord neurons by influencing the ligand-gated (GABA and glutamate) channels.
Foroutan
A
A
Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Ohio 45267-0576, USA.
Behbehan
M M
MM
Anderson
D K
DK
D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D018756:GABA Antagonists / Q000378:metabolism*; D005938:Glucocorticoids; D018698:Glutamic Acid / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008775:Methylprednisolone / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D018756:GABA Antagonists; D005938:Glucocorticoids; D018696:Neuroprotective Agents; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D008775:Methylprednisolone