Coadministered nitrous oxide enhances the effect of isoflurane on GABAergic transmission by an increase in open-channel block
G Hapfelmeier1, R Haseneder, E Kochs
1Department of Anaesthesiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. hapfelmeier@mpipskyl.mpg.de
Abstract:
Clinically relevant concentrations of isoflurane (ISO) and nitrous oxide (N2O) enhance chloride currents induced by activating gamma-aminobutyric acid(A) receptors (GABA(A)R). Channel blocking by ISO overcomes the enhancing effect at higher concentrations. In this study, the effect of coadministered ISO and N2O on responses evoked by GABA in transfected human embryonic kidney 293 cells carrying alpha1beta2gamma2L GABA(A)R was investigated. Patch-clamp recordings from these cells were performed in the whole cell mode. A piezo-driven "liquid filament" drug application system was used to apply solutions of GABA, ISO, and N2O. Increasing the concentration of ISO in steps from 0.15 to 1.2 mM resulted in a bell-shaped concentration-response curve for GABA-induced currents. The maximum increase in current (1.51 +/- 0.14-fold) was seen at 0.45 mM ISO (about 1 minimum alveolar concentration, EC50). N2O (29.2 mM) increased GABA-evoked currents 1.54 +/- 0.10-fold. The enhancing effects of ISO and N2O on the GABAergic response were not additive. However, a transient current, associated with the rapid withdrawal of ISO from the receptor, was markedly increased by N2O. Such rebound currents probably reflect the transition from a "channel-blocked" to a "reopened" state. An open-channel block at ligand-gated receptors can prolong postsynaptic currents. Thus, we conclude that coadministered N2O could increase the enhancing effect of ISO on the GABAergic transmission by an increase in open-channel block at the GABA(A)R.
More Related Videos
08:16Optogenetic Activation of Afferent Pathways in Brain Slices and Modulation of Responses by Volatile Anesthetics
Published on: July 23, 2020
09:36Halogenated Agent Delivery in Porcine Model of Acute Respiratory Distress Syndrome via an Intensive Care Unit Type Device
Published on: September 24, 2020
Related Concept Videos
Inhalational Anesthetics: Overview
Parenteral Anesthetics: Overview
General Anesthesia: Overview
General anesthesia induces unconsciousness in the whole body, while the others target specific areas or sensations. It is administered to minimize adverse effects, maintain...
Local Anesthetics: Mechanism of Action
Local anesthetics are amphiphilic molecules consisting of a hydrophobic aromatic part linked to a hydrophilic group by an ester or amide linkage. They are weak bases and are usually available as salts, which increases their solubility and stability. Once administered, LAs exist in the body either...
Local Anesthetics: Clinical Application as Surface, Infiltration, and Conduction Block Anesthesia
Local Anesthetics: Clinical Application as Epidural Anesthesia
Since epidural anesthetics can be infused through an epidural catheter, all types of drugs, including short-acting ones, can be administered. Chloroprocaine and lidocaine are examples of short and long-duration anesthetics, respectively. Bupivacaine...
