QUATERNARY STRUCTURE OF THE NATIVE GABA(A) RECEPTOR DETERMINED BY ELECTRON-MICROSCOPIC IMAGE-ANALYSIS

In the transmitter-gated ion channel class of receptors, the members o f which are all believed to be heterooligomers, the number and arrange ment of the subunits are only known with any certainty for the nicotin ic acetylcholine receptor from Torpedo electric fish. That receptor ha s been shown to possess a pentameric rosette structure, with five homo logous subunits (alpha(2) beta(g)amma delta) arranged to enclose the c entral ion channel. The data were obtained by electron image analysis of two-dimensional receptor arrays, which form as a consequence of tha t receptor's exceptionally high abundance in the Torpedo membranes and are therefore not attainable for other receptors. We have applied ano ther direct approach to determine the quaternary structure of native i onotropic GABA receptors. We have purified those receptors from porcin e brain cortex and analysed the rotational symmetry of isolated recept ors visualized by electron microscopy. The results show the receptor t o have a pentameric structure with a central water-filled pore, which can now be said to be characteristic of the entire superfamily.