Non-GABAergic effects of midazolam, diazepam and flumazenil on voltage-dependent ion currents in NG108-15 cells.
Non-gamma-Aminobutyric acid (GABA)-mediated effects of benzodiazepines (BZs) have not been widely investigated. However, there is significant evidence in the literature to suggest that several experimental and clinical observations are inconsistent with the commonly accepted GABAergic mechanisms of action for these drugs. The purpose of the present study was to explore electrophysiological effects of midazolam, diazepam and a specific BZ antagonist, flumazenil, using patch-clamp techniques in NG108-15 cells which do not express the GABAA receptor. Midazolam and diazepam decreased Na+, K+ and Ca2+ currents in a dose-related manner. Ca2+ currents were reduced more significantly by diazepam than by midazolam. Flumazenil showed no effects on voltage-dependent ion currents. GABA by itself showed neither effects on the membrane potential nor these ion currents. Midazolam and diazepam, but not flumazenil, exhibited effects on voltage-dependent ion currents in cultured neurons.
Ishizawa
Y
Y
Department of Anesthesiology and Critical Care Medicine, Gifu University School of Medicine, Japan.
Furuya
K
K
Yamagishi
S
S
Dohi
S
S
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology*; D005910:Glioma; D006822:Hybrid Cells; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D008874:Midazolam / Q000494:pharmacology*; D009447:Neuroblastoma; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011963:Receptors, GABA-A / Q000502:physiology; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D015220:Calcium Channels; D007473:Ion Channels; D015221:Potassium Channels; D011963:Receptors, GABA-A; D015222:Sodium Channels; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D003975:Diazepam; D008874:Midazolam