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Originally published In Press as doi:10.1074/jbc.M513447200 on June 7, 2006

J. Biol. Chem., Vol. 281, Issue 34, 24204-24215, August 25, 2006
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The Metabotropic Glutamate G-protein-coupled Receptors mGluR3 and mGluR1a Are Voltage-sensitive*

Lily Ohana, Ofra Barchad, Itzchak Parnas, and Hanna Parnas1

From the Department of Neurobiology, the Hebrew University, Jerusalem 91904, Israel

G-protein-coupled receptors play a key role in signal transduction processes. Despite G-protein-coupled receptors being transmembrane proteins, the notion that they exhibit voltage sensitivity is rather novel. Here we examine whether two metabotropic glutamate receptors, mGluR3 and mGluR1a, both involved in fundamental physiological processes, exhibit, by themselves, voltage sensitivity. Measuring mGluR3-induced K+ currents and mGluR1a-induced Ca2+-activated Cl currents in Xenopus oocytes, we show that the apparent affinity toward glutamate decreases (mGluR3) or increases (mGluR1a) upon depolarization. Measurements of binding of [3H]glutamate to oocytes expressing either mGluR3 or mGluR1a corroborated the electrophysiological results. Using the chimeric G{alpha} subunit, we further show that the voltage sensitivity does not reside in the G-protein. To locate sites within the receptors that are involved in the voltage sensitivity, we used chimeric mGluR1a, where the intracellular loops that couple to the G-protein were replaced by those of mGluR3. The voltage sensitivity of the chimeric mGluR1a resembled that of mGluR3 and not that of the parental mGluR1a. The cumulative results indicate that the voltage sensitivity does not reside downstream to the activation of the receptors but rather in the mGluR3 and mGluR1a themselves. Furthermore, the intracellular loops play a crucial role in relaying changes in membrane potential to changes in the affinity of the receptors toward glutamate.


Received for publication, December 19, 2005 , and in revised form, May 22, 2006.

* This work was supported by Deutsche Forschungsgemeinschaft Grant SFB 391 (to Profs. J. Dudel, I. P., and H. P.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 To whom all correspondence should be addressed: Dept. of Neurobiology, The Hebrew University, Jerusalem 91904, Israel. Tel.: 972-2-6585900; Fax: 972-2-6584174; E-mail: hanna{at}vms.huji.ac.il.


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