Selective Enhancement of Tonic GABAergic Inhibition in Murine Hippocampal Neurons by Low Concentrations of the Volatile Anesthetic Isoflurane

• Published in: The Journal of neuroscience Vol. 24; no. 39; pp. 8454 - 8458
• Main Authors: Caraiscos, Valerie B, Newell, J. Glen, You-Ten, Kong E, Elliott, Erin M, Rosahl, Thomas W, Wafford, Keith A, MacDonald, John F, Orser, Beverley A
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 29.09.2004; Society for Neuroscience
• Subjects: Anesthetics, Inhalation - pharmacology; Animals; Brief Communications; Cells, Cultured; Cerebral Cortex - cytology; Dose-Response Relationship, Drug; Evoked Potentials - drug effects; Excitatory Postsynaptic Potentials - drug effects; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - physiology; Isoflurane - pharmacology; Mice; Mice, Knockout; Neural Inhibition - drug effects; Pyramidal Cells - drug effects; Pyramidal Cells - physiology; Receptors, GABA-A - drug effects; Receptors, GABA-A - genetics; Receptors, GABA-A - physiology; Recombinant Proteins; Synaptic Transmission - drug effects
• DOI: 10.1523/JNEUROSCI.2063-04.2004
• ISSN: 0270-6474; 1529-2401

Volatile (inhaled) anesthetics cause amnesia at concentrations well below those that cause loss of consciousness and immobility; however, the underlying neuronal mechanisms are unknown. Although many anesthetics increase inhibitory GABAergic synaptic transmission, this effect occurs only at high concentrations (>100 μ m ). Molecular targets for low concentrations of inhaled anesthetics have not been identified. Here, we report that a tonic inhibitory conductance in hippocampal pyramidal neurons generated by α5 subunit-containing GABA A receptors is highly sensitive to low concentrations of the volatile anesthetic isoflurane (ISO) (25 and 83.3 μ m ). The α5 subunit is necessary for enhancement of the tonic current by these low concentrations of isoflurane because potentiation is absent in neurons from α5 -/- mice. Furthermore, ISO (25 μ m ) potentiated recombinant human α5β3γ2L GABA A receptors, whereas this effect was not seen with α1β3γ2L GABA A receptors. These studies suggest that an increased tonic inhibition in the hippocampus may contribute to amnestic properties of volatile anesthetics.