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Receptor kinase‐dependent desensitization of the muscarinic K+ current in rat atrial cells.
Author(s) -
Shui Z,
Boyett M R,
Zang W J,
Haga T,
Kameyama K
Publication year - 1995
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1995.sp020885
Subject(s) - muscarinic acetylcholine receptor , desensitization (medicine) , homologous desensitization , intracellular , protein kinase c , biophysics , chemistry , microbiology and biotechnology , protein kinase a , muscarinic acetylcholine receptor m2 , muscarinic acetylcholine receptor m3 , receptor , carbachol , patch clamp , acetylcholine , kinase , endocrinology , biology , medicine , biochemistry
1. Activity of rat atrial muscarinic K+ channels has been measured in five configurations of the patch clamp technique. 2. In configurations in which the normal intracellular solution was lost, the slow phase of desensitization (a slow decline of channel activity during an exposure to ACh) was much reduced (or absent) and deactivation (on wash‐off of ACh) was slowed as compared with desensitization and deactivation in configurations in which normal intracellular solution was retained. This suggests that soluble intracellular regulators are involved in these processes. 3. When a G protein‐coupled receptor kinase (GRK2) was applied to the cytoplasmic surface of conventional outside‐out patches in the presence of ATP, the slow phase of desensitization was restored. In the absence of ATP, GRK2 failed to restore the slow phase. 4. It is concluded that (i) G protein‐coupled receptor kinase dependent phosphorylation of the muscarinic receptor is responsible for the slow phase of desensitization and (ii) a soluble factor (such as a GTPase activating protein or ‘GAP’) is responsible for normal rapid deactivation.