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Direct voltage control of endogenous lysophosphatidic acid G‐protein‐coupled receptors in Xenopus oocytes
Author(s) -
MartinezPinna Juan,
Gurung Iman S.,
MahautSmith Martyn P.,
Morales Andrés
Publication year - 2010
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2009.183418
Subject(s) - depolarization , lysophosphatidic acid , agonist , g protein coupled receptor , xenopus , membrane potential , biophysics , microbiology and biotechnology , chemistry , receptor , g protein , biology , intracellular , signal transduction , biochemistry , gene
Lysophosphatidic acid (LPA) G‐protein‐coupled receptors (GPCRs) play important roles in a variety of physiological and pathophysiological processes, including cell proliferation, angiogenesis, central nervous system development and carcinogenesis. Whilst many ion channels and transporters are recognized to be controlled by a change in cell membrane potential, little is known about the voltage dependence of other proteins involved in cell signalling. Here, we show that the Ins P 3 ‐mediated Ca 2+ response stimulated by the endogenous LPA GPCR in Xenopus oocytes is potentiated by membrane depolarization. Depolarization was able to repetitively stimulate transient [Ca 2+ ] i increases after the initial agonist‐evoked response. In addition, the initial rate and amplitude of the LPA‐dependent Ca 2+ response were significantly modulated by the steady holding potential over the physiological range, such that the response to LPA was potentiated at depolarized potentials and inhibited at hyperpolarized potentials. Enhancement of LPA receptor‐evoked Ca 2+ mobilization by membrane depolarization was observed over a wide range of agonist concentrations. Importantly, the amplitude of the depolarization‐evoked intracellular Ca 2+ increase displayed an inverse relationship with agonist concentration such that the greatest effect of voltage was observed at near‐threshold levels of agonist. Voltage‐dependent Ca 2+ release was not induced by direct elevation of Ins P 3 or by activation of heterotrimeric G‐proteins in the absence of agonist, indicating that the LPA GPCR itself represents the primary site of action of membrane voltage. This novel modulation of LPA signalling by membrane potential may have important consequences for control of Ca 2+ signals both in excitable and non‐excitable tissues.