IK.ACh activation by arachidonic acid occurs via a G-protein-independent pathway mediated by the GIRK1 subunit.
The molecular target of arachidonic-acid-derived metabolites, serving as second messengers that activate atrial acetylcholine-activated potassium current (IK.ACh) in addition to G-protein beta/gamma subunits (Gbeta/gamma), is unknown. Co-expression of two isoforms of G-protein-activated, inwardly rectifying potassium channels (GIRKs) in oocytes of Xenopus laevis revealed that these heterologous co-expressed GIRKs, which are responsible for the formation of IK.ACh in the atrium, are activated by arachidonic acid metabolites, like their counterparts in atrial cells. The expression of homooligomeric GIRK1(F137S) and GIRK4wt channels revealed that this activatory mechanism is specific to the GIRKI subunit. Sequestrating available Gbeta/gamma by overexpression of C-betaARK (a Gbeta/gamma binding protein) failed to abolish the activation of GIRK currents by arachidonic acid. From our experiments we conclude that the GIRKI subunit itself is the molecular target for regulation of GIRK channels by arachidonic acid metabolites.
Lohberger
B
B
Institute for Medical Physics and Biophysics, University of Graz, Austria.
Groschner
K
K
Tritthart
H
H
Schreibmayer
W
W
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics; D004553:Electric Conductivity; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D019204:GTP-Binding Proteins / Q000502:physiology*; D015870:Gene Expression; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D009865:Oocytes / Q000502:physiology; D010446:Peptide Fragments / Q000235:genetics; D015221:Potassium Channels / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D011976:Receptors, Muscarinic / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins; D014162:Transfection; D014982:Xenopus laevis
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D016376:Oligonucleotides, Antisense; D010446:Peptide Fragments; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011976:Receptors, Muscarinic; D011994:Recombinant Proteins; D016718:Arachidonic Acid; D017868:Cyclic AMP-Dependent Protein Kinases; C114043:BARKct protein, recombinant; D019204:GTP-Binding Proteins; D000109:Acetylcholine