Quaternary Structure of the Native GABAA Receptor Determined by Electron Microscopic Image Analysis


Address correspondence and reprint requests to Prof. E. A. Barnard at his present address: Molecular Neurobiology Unit, Division of Basic Medical Sciences, Royal Free Hospital School of Medicine, London, U.K.


Abstract: In the transmitter-gated ion channel class of receptors, the members of which are all believed to be heterooligomers, the number and arrangement of the subunits are only known with any certainty for the nicotinic acetylcholine receptor from Torpedo electric fish. That receptor has been shown to possess a pentameric rosette structure, with five homologous subunits (α2βγδ) arranged to enclose the central ion channel. The data were obtained by electron image analysis of two-dimensional receptor arrays, which form as a consequence of that receptor's exceptionally high abundance in the Torpedo membranes and are therefore not attainable for other receptors. We have applied another direct approach to determine the quaternary structure of native ionotropic GABA receptors. We have purified those receptors from porcine brain cortex and analysed the rotational symmetry of isolated receptors visualized by electron microscopy. The results show the receptor to have a pentameric structure with a central water-filled pore, which can now be said to be characteristic of the entire superfamily.