G protein‐activated K+ channels: a reporter for rapid activation of G proteins by lysophosphatidic acid in Xenopus oocytes

Threshold concentrations of lysophosphatidic acid (LPA) or acetylcholine (ACh) induce pertussis toxin (PTX)- sensitive rapid desensitization of responses to LPA in Xenopus oocytes. To demonstrate that threshold (LPA) rapidly activates Gi/o proteins, we used the G protein-activated K + channel (GIRK) as a reporter. Low (LPA) induced IK+ in 6 3 s of the agonist addition with little or no activation of chloride current. Depletion of GKo/GK Ko1 each decreased the LPA-induced IK+ by approximately 40^50%, while PTX completely abolished it. This is the ¢rst direct evidence showing the activation of GIRK by LPA, and the involvement of G proteins of the Go family in rapid desensitization of LPA responses. 4 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.