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Anesthesiology. 2014 Jul;121(1):68-78. doi: 10.1097/ALN.0000000000000183.

Fast-spiking cell to pyramidal cell connections are the most sensitive to propofol-induced facilitation of GABAergic currents in rat insular cortex.

Author information

1
From the Department of Anesthesiology (Y.K., Y.O.), and Department of Pharmacology (K.Y., N.K., M.K.), Nihon University School of Dentistry, Tokyo, Japan; Division of Immunology and Pathobiology (Y.K., Y.O.), and Division of Oral and Craniomaxillofacial Research (K.Y., N.K., M.K.), Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan; and Molecular Dynamics Imaging Unit, RIKEN Center for Life Science Technologies, Kobe, Japan (M.K.).

Abstract

BACKGROUND:

Propofol facilitates γ-aminobutyric acid-mediated inhibitory synaptic transmission. In the cerebral cortex, γ-aminobutyric acidergic interneurons target both excitatory pyramidal cells (Pyr) and fast-spiking (FS) and non-FS interneurons. Therefore, the propofol-induced facilitation of inhibitory transmission results in a change in the balance of excitatory and inhibitory inputs to Pyr. However, it is still unknown how propofol modulates γ-aminobutyric acidergic synaptic transmission in each combination of Pyr and interneurons.

METHODS:

The authors examined whether propofol differentially regulates inhibitory postsynaptic currents (IPSCs) depending on the presynaptic and postsynaptic cell subtypes using multiple whole cell patch clamp recording from γ-aminobutyric acidergic interneurons and Pyr in rat insular cortex.

RESULTS:

Propofol (10 μM) consistently prolonged decay kinetics of unitary IPSCs (uIPSCs) in all types of inhibitory connections without changing paired-pulse ratio of the second to first uIPSC amplitude or failure rate. The FS→Pyr connections exhibited greater enhancement of uIPSC charge transfer (2.2 ± 0.5 pC, n = 36) compared with that of FS→FS/non-FS connections (0.9 ± 0.2 pC, n = 37), whereas the enhancement of charge transfer in non-FS→Pyr (0.3 ± 0.1 pC, n = 15) and non-FS→FS/non-FS connections (0.2 ± 0.1 pC, n = 36) was smaller to those in FS→Pyr/FS/non-FS. Electrical synapses between FS pairs were not affected by propofol.

CONCLUSIONS:

The principal inhibitory connections (FS→Pyr) are the most sensitive to propofol-induced facilitation of uIPSCs, which is likely mediated by postsynaptic mechanisms. This preferential uIPSC enhancement in FS→Pyr connections may result in suppressed neural activities of projection neurons, which in turn reduces excitatory outputs from cortical local circuits.

PMID:
24577288
DOI:
10.1097/ALN.0000000000000183
[Indexed for MEDLINE]

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