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 <3 s of the agonist addition with little or no activation of chloride current. Depletion of Galphao/Galphao1 each decreased the LPA-induced IK+ by approximately 40-50%, while PTX completely abolished it. This is the first 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.
Itzhaki Van-Ham
Irit
I
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel.
Peleg
Sagit
S
Dascal
Nathan
N
Shapira
Hagit
H
Oron
Yoram
Y
D000818:Animals; D004594:Electrophysiology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D008246:Lysophospholipids / Q000494:pharmacology*; D008564:Membrane Potentials; D008845:Microinjections; D009865:Oocytes; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000819:agonists* / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D012377:Rodentia; D014981:Xenopus
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D008246:Lysophospholipids; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D019204:GTP-Binding Proteins; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; C032881:lysophosphatidic acid; D011188:Potassium