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J. Biol. Chem., Vol. 276, Issue 15, 11691-11697, April 13, 2001

This Article Full Text Full Text (PDF) All Versions of this Article: 276/15/11691    most recent M011007200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shui, Z. Articles by Boyett, M. R. Search for Related Content PubMed PubMed Citation Articles by Shui, Z. Articles by Boyett, M. R. Social Bookmarking                      What's this?

Control of the Cardiac Muscarinic K⁺ Channel by -Arrestin 2^*

Z. Shui, I. A. Khan, T. Haga, J. L. Benovic^§, and M. R. Boyett^¶

From the School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom, the  Department of Neurochemistry, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Tokyo 113-0033, Japan, and the ^§ Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107

Control of the cardiac muscarinic K⁺ current (i_K,ACh) by -arrestin 2 has been studied. In Chinese hamster ovary cells transfected with m2 muscarinic receptor, muscarinic K⁺ channel, receptor kinase (GRK2), and -arrestin 2, desensitization of i_K,ACh during a 3-min application of 10 µM ACh was significantly increased as compared with that in cells transfected with receptor, channel, and GRK2 only (fade in current increased from 45 to 78%). The effect of -arrestin 2 was lost if cells were not co-transfected with GRK2. Resensitization (recovery from desensitization) of i_K,ACh in cells transfected with -arrestin 2 was significantly slowed (time constant increased from 34 to 232 s). Activation and deactivation of i_K,ACh on application and wash-off of ACh in cells transfected with -arrestin 2 were significantly slowed from 0.9 to 3.1 s (time to half peak i_K,ACh) and from 6.2 to 13.8 s (time to half-deactivation), respectively. In cells transfected with a constitutively active -arrestin 2 mutant, desensitization occurred in the absence of agonist (peak current significantly decreased from 0.4 ± 0.05 to 0.1 ± 0.01 nA). We conclude that -arrestin 2 has the potential to play a major role in desensitization and other aspects of the functioning of the muscarinic K⁺ channel.

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