Antisense oligonucleotides against receptor kinase GRK2 disrupt target selectivity of beta-adrenergic receptors in atrial myocytes.
K+ channels composed of GIRK subunits are predominantly expressed in the heart and various regions of the brain. They are activated by betagamma-subunits released from pertussis toxin-sensitive G-proteins coupled to different seven-helix receptors. In rat atrial myocytes, activation of K(ACh) channels is strictly limited to receptors coupled to pertussis toxin-sensitive G-proteins. Upon treatment of myocytes with antisense oligodesoxynucleotides against GRK2, a receptor kinase with Gbetagamma binding sites, in a fraction of cells, K(ACh) channels can be activated by beta-adrenergic receptors. Sensitivity to beta-agonist is insensitive to pertussis toxin treatment. These findings demonstrate a potential role of Gbetagamma binding proteins for target selectivity of G-protein-coupled receptors.
Wellner-Kienitz
M C
MC
Institut für Physiologie, Abteilung Zelluläre Physiologie, Ruhr-Universität Bochum, Germany.
Bender
K
K
Brandts
B
B
Meyer
T
T
Pott
L
L
D000818:Animals; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D006325:Heart Atria / Q000378:metabolism*; D015640:Ion Channel Gating / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology*; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011921:Rats, Inbred WKY; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D051552:beta-Adrenergic Receptor Kinases
D016376:Oligonucleotides, Antisense; D015221:Potassium Channels; D011943:Receptors, Adrenergic, beta; D017868:Cyclic AMP-Dependent Protein Kinases; D051552:beta-Adrenergic Receptor Kinases