General Anesthetic Effects on GABA_A Receptors

Adequate hypnosis at very low isoflurane concentration during craniotomy monitored by electroencephalography

“…Of these factors, we propose a mechanism of clonazepamisofl urane interaction. While clonazepam acts at the interface between the α and γ subunits of γ-aminobutyric acid (GABA) A receptors, isofl urane acts at the TM 1 , TM 2 , and TM 3 domains of the transmembrane regions of the same GABA A receptors [10]. Because both agents act at different parts of the same receptor, there could have been a synergistic interaction between the two, resulting in adequate hypnosis even at a low isofl urane concentration.…”

Molecular mechanisms of general anesthesia

“…The free neurotransmitters bind with ion channel receptors to control the flow of ions. The control of cell electrical activity by ion channels is closely linked with the physiologic action of anesthetics and the various behavioral response patterns to them (Table 1) [11]. Among ion channels, GABA A , glycine, nicotinic acetylcholine, and N-methyl-D-aspartate (NMDA) receptors show sensitivity to general anesthetics [1-4].…”

“…Some of the volatile anesthetics also act on potassium channels and voltage-gated channels (sodium, calcium) [12-14]. Typically, general anesthetics potentiate the activation of inhibitory postsynaptic channels or inhibit the activation of excitatory synaptic channels [11]. …”

“…Most inhibition is mediated by GABA A receptors, which are chloride-permeable ligand-gated ion channels. Activation of GABA A receptors generally leads to an influx of chloride, hyperpolarization of the cell membrane, shunting of excitatory input, and reduced excitability of the neurons [11]. The GABA A receptor itself is a heteropentameric complex composed of five different subunits, and 19 subunits (α 1-6 , β 1-3 , γ 1-3 , δ, ε, ψ, π and ρ 1-3 ) have been known until now [16].…”