Role of receptor kinase in short‐term desensitization of cardiac muscarinic K+ channels expressed in Chinese hamster ovary cells

Abstract

1 The cardiac muscarinic receptor‐K⁺ channel system was reconstructed in Chinese hamster ovary (CHO) cells by transfecting the cells with the various components of the system. The activity of the muscarinic K⁺ channel was measured with the cell‐attached configuration of the patch clamp technique. 2 In CHO cells transfected with the channel (Kir3.1/Kir3.4), receptor (hm2) and receptor kinase (GRK2), on exposure to agonist, there was a decline in channel activity as a result of desensitization, similar to that in atrial cells. 3 Whereas the desensitization was almost abolished by not transfecting with the receptor kinase or by transfecting with a mutant receptor lacking phosphorylation sites, it was only reduced (by ≈39 %) by transfecting with a mutant receptor kinase with little kinase activity. 4 These results suggest that the receptor kinase is responsible for desensitization of the muscarinic K⁺ channel and that this involves phosphorylation‐dependent and ‐independent mechanisms.