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

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 (a2ßyS) 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 . Key Words: GABAA receptor-Electron microscopy-Image analysis-Quaternary structure. J. Neurochem . 62, 815-818 (1994) .

Identification of ion channel genes in the Acyrthosiphon pisum genome

“…Both GABA and glycine receptors belong to the dicysteine-loop ('Cysloop') superfamily of neurotransmitter receptors (Grenningloh et al, 1987;Schofield et al, 1987). These chloride channels are pentameric (Nayeem et al, 1994) and they are the target of cyclodiene and phenylpyrazole insecticides.…”

Alternate Use of Distinct Intersubunit Contacts Controls GABAAReceptor Assembly and Stoichiometry

“…GABA A receptors are hetero-oligomeric proteins consisting of five subunits (Nayeem et al, 1994;Tretter et al, 1997). So far at least 19 GABA A receptor subunits belonging to several subunit classes (six ␣, three ␤, three ␥, one ␦, one ⑀, one , one , and three ) have been identified in mammalian brain (Barnard et al, 1998;Sieghart et al, 1999).…”

Classics in Chemical Neuroscience: Diazepam (Valium)

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