ABSTRACT
Molecular cloning of cDNAs coding for ligand-gated ion channel subunits makes it possible to study the pharmacology of recombinant receptors with defined subunit compositions. Many laboratories have used these techniques recently to study actions of agents that produce general anesthesia. Most of the volatile and intravenous anesthetics potentiate the function of GABAA receptor to different extent. Glycine, AMPA, kainate,NMDA, and 5-HT3 recepors are also the targets for many anesthetics. Subunit specific actions of some of the agents suggest that construction and testing of certain chimeric receptor subunits may be useful for defining the amino acid sequences responsible for anesthetic actions.
ABSTRACT
In addition to modulation by a variety of structurally diverse agents that act allosteri-cally via distinct binding sites on the receptor complexes , there is another outstanding characteristic of the GABAA receptors: they are modulated by multiple endogenous agents. Well known examples include Ca2+ , adenosine triphosphate (ATP) , protein kinase A (PKA), protein kinase C(PKC), ty-ros ine kinase (TK) and calmodulin-dependent protein kinase II (CaMK II ). Intracellular modulation of GABAA receptor function may have profound effects on the control of neuronal excitation.