Many structurally diverse general anaesthetics enhance inhibitory neurotransmission in the central nervous system by interacting with the GABA(A) receptor. By contrast, GABA receptors composed of the ρ1 subunit are anaesthetic-insensitive. Here, we demonstrate that both δ-hexachlorocyclohexane (δ-HCH; 1-100 μM), a positive allosteric modulator of the GABA(A) receptor, and the anaesthetic pentobarbitone (10-600 μM) have no effect on GABA-evoked currents mediated by wild-type ρ1 recombinant receptors (expressed in Xenopus laevis oocytes). By contrast, these agents produce up to a 10 fold enhancement of GABA responses transduced by a ρ1 receptor in which a transmembrane located isoleucine residue is replaced by serine. However, not all general anaesthetics were similarly influenced by this mutation, because propofol and 5β-pregnan-3α-ol-20-one (5β3α) remained ineffective. These data are discussed in relation to the specificity of general anaesthetic action.
- GABA(A) receptor
- General anaesthetic