ROLE OF RECEPTOR KINASE IN SHORT-TERM DESENSITIZATION OF CARDIAC MUSCARINIC K-HAMSTER OVARY CELLS( CHANNELS EXPRESSED IN CHINESE)

1. The cardiac muscarinic receptor-K+ channel system was reconstructed in Chinese hamster ovary (CHO) cells by transfecting the cells with t he various components of the system. The activity of the muscarinic K channel was measured with the cell-attached configuration of the patc h clamp technique. 2. In CHO cells transfected with the channel (Kir3. 1/Kir3.4), receptor (hm2) and receptor kinase (GRK2), on exposure to a gonist, there was a decline in channel activity a a result of desensit ization, similar to that in atrial cells. 3. Whereas the desensitizati on was almost abolished by not transfecting with the receptor kinase o r by transfecting with a mutant receptor lacking phosphorylation sites , it was only reduced (by similar to 39%) by transfecting with a mutan t receptor kinase with little kinase activity. 4. These results sugges t that the receptor kinase is responsible for desensitization of the m uscarinic K+ channel and that this involves phosphorylation-dependent and -independent mechanisms.