RT Journal Article
SR Electronic
T1 Selective Enhancement of Tonic GABAergic Inhibition in Murine Hippocampal Neurons by Low Concentrations of the Volatile Anesthetic Isoflurane
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8454
OP 8458
DO 10.1523/JNEUROSCI.2063-04.2004
VO 24
IS 39
A1 Valerie B. Caraiscos
A1 J. Glen Newell
A1 Kong E. You-Ten
A1 Erin M. Elliott
A1 Thomas W. Rosahl
A1 Keith A. Wafford
A1 John F. MacDonald
A1 Beverley A. Orser
YR 2004
UL http://www.jneurosci.org/content/24/39/8454.abstract
AB 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 μm). 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 GABAA receptors is highly sensitive to low concentrations of the volatile anesthetic isoflurane (ISO) (25 and 83.3 μm). 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 μm) potentiated recombinant human α5β3γ2L GABAA receptors, whereas this effect was not seen with α1β3γ2L GABAA receptors. These studies suggest that an increased tonic inhibition in the hippocampus may contribute to amnestic properties of volatile anesthetics.