General anesthetic actions on GABA(A) receptors

Abstract

General anesthetic drugs interact with many receptors in the nervous system, but only a handful of these interactions are critical for producing anesthesia. Over the last 20 years, neuropharmacologists have revealed that one of the most important target sites for general anesthetics is the GABA(A) receptor. In this review we will discuss what is known about anesthetic - GABA(A) receptor interactions.

Keywords: Barbiturates.; Desflurane; Etomidate; GABAA Receptor; General Anesthetic; Isoflurane; Propofol; Sevoflurane.

Fig. (1)

Examples of chloride currents for α₁β₂γ_2s, α₅β₂γ_2s, and α₆β₂γ_2s GABA_A receptors. Left panels show representative whole-cell recordings achieved by applications of increasing concentrations of GABA (black bars). Right panels show paired recordings with the same concentrations of GABA in the presence of 2 MAC isoflurane (blue bar). GABA concentrations (all in µM) for α₁β₂γ_2s GABA_A receptors (0.3, 1, 3, 10, 30, 100, 300, 1000), for α₅β₂γ_2s GABA_A receptors (0.1, 0.3, 1, 3, 10, 30, 100, 300), and for α₆β₂γ_2s GABA_A receptors (0.1, 0.3, 1, 3, 10, 30, 100). Vertical scale bars 100 pA; Horizontal scale bars 10 s. The data indicate that α₆ containing receptors are more sensitive to low concentrations of anesthetic than α₁β₂γ_2s, or ;₅β₂γ_2s receptors and that isoflurane is more effective at reducing the apparent affinity of GABA at α₅ containing receptors than at α₁β₂γ_2s, or α₆β₂γ_2s GABA_A receptors. The methods used to collect these results have been described previously [59].