Antisense oligonucleotides against receptor kinase GRK2 disrupt target selectivity of β‐adrenergic receptors in atrial myocytes

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Abstract
K+ channels composed of GIRK subunits are predominantly expressed in the heart and various regions of the brain. They are activated by βγ‐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 Gβγ binding sites, in a fraction of cells, K(ACh) channels can be activated by β‐adrenergic receptors. Sensitivity to β‐agonist is insensitive to pertussis toxin treatment. These findings demonstrate a potential role of Gβγ binding proteins for target selectivity of G‐protein‐coupled receptors