Serum-induced membrane depolarization in quiescent fibroblasts: activation of a chloride conductance through the G protein-coupled LPA receptor

EMBO J. 1996 Jan 2;15(1):63-72.


Serum stimulation of quiescent fibroblasts leads to a dramatic depolarization of the plasma membrane; however, the identity of the active serum factor(s) and the underlying mechanism are unknown. We find that this serum activity is attributable to albumin-bound lysophosphatidic acid (LPA) acting on its own G protein-coupled receptor, and that membrane depolarization is due to activation of an anion conductance mediating Cl- efflux. This depolarizing Cl- current can also be activated by thrombin and neuropeptide receptors; it is distinct from volume-regulated Cl- currents. Activation of the Cl- current consistently follows stimulation of phospholipase C and coincides with remodelling of the actin cytoskeleton, which is regulated by the Ras-related GTPase Rho. However, the response is not due to Ca2+/protein kinase C signalling and requires neither Rho nor Ras activation. The results indicate that in quiescent fibroblasts, LPA and other G protein-coupled receptor agonists evoke membrane depolarization by activating a new type of Cl- channel through a signalling pathway that is closely associated with phosphoinositide hydrolysis, yet independent of known second messengers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Size
  • Cells, Cultured
  • Chloride Channels / physiology*
  • Chlorides / physiology
  • Fibroblasts
  • GTP-Binding Proteins / metabolism
  • GTP-Binding Proteins / physiology
  • Ion Channel Gating
  • Membrane Potentials
  • Rats
  • Receptors, Cell Surface / physiology*
  • Receptors, G-Protein-Coupled*
  • Receptors, Lysophosphatidic Acid
  • Serum Albumin / physiology*
  • Type C Phospholipases / physiology
  • rho GTP-Binding Proteins


  • Chloride Channels
  • Chlorides
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Receptors, Lysophosphatidic Acid
  • Serum Albumin
  • Type C Phospholipases
  • GTP-Binding Proteins
  • rho GTP-Binding Proteins