Interaction of the neuroprotective drug riluzole with GABA A and glycine receptor channels

• Published in: European journal of pharmacology 2001-03, Vol.415 (2), p.135-140
• Main Authors: Mohammadi, Bahram, Krampfl, Klaus, Moschref, Hafis, Dengler, Reinhard, Bufler, Johannes
• Format: Article
• Language: English
• Subjects: Cell Line; Dose-Response Relationship, Drug; GABA A receptor channel; gamma-Aminobutyric Acid - pharmacology; Glycine - pharmacology; Glycine receptor channel; Humans; Kidney - cytology; Neuroprotective Agents - pharmacology; Patch-Clamp Techniques; Patch–clamp technique; Rapid application; Receptors, GABA-A - drug effects; Receptors, GABA-A - physiology; Receptors, Glycine - drug effects; Receptors, Glycine - physiology; recombinant α 1β; recombinant α 1β 2γ 2; Riluzole; Riluzole - pharmacology
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(01)00847-0

Riluzole is used as therapeutic agent in amyotrophic lateral slerosis. We investigated the interaction of riluzole with recombinant GABA (γ-aminobutyric acid) A receptor channels (α 1β 2γ 2-subunits) and glycine receptor channels (α 1β-subunits) transiently expressed in HEK293 cells. For electrophysiological experiments, the patch–clamp technique in combination with tools for ultrafast solution exchange was used. Saturating concentrations of GABA or glycine were applied with different concentrations of riluzole to outside-out patches containing α 1β 2γ 2 GABA A receptor channels or α 1β-glycine receptor channels on their surface, respectively. The current declined after application of GABA or glycine with three time constants of desensitization to a steady-state current amplitude. Application of riluzole resulted in a shift to fast desensitized states at both receptors. The proportion of the time constants of fast desensitization increased and the time constants of slow desensitization and the steady-state current decreased whereas the maximal current amplitudes were not affected by riluzole. The data of the study demonstrate for the first time interaction of GABAergic and glycinergic currents with riluzole under physiological conditions.