Control of the cardiac muscarinic K+current (iK,ACh) by β-arrestin 2 has been studied. In Chinese hamster ovary cells transfected with m2 muscarinic receptor, muscarinic K+channel, receptor kinase (GRK2), and β-arrestin 2, desensitization of iK,AChduring a 3-min application of 10 μmACh 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 β-arrestin 2 was lost if cells were not co-transfected with GRK2. Resensitization (recovery from desensitization) of iK,AChin cells transfected with β-arrestin 2 was significantly slowed (time constant increased from 34 to 232 s). Activation and deactivation of iK,AChon application and wash-off of ACh in cells transfected with β-arrestin 2 were significantly slowed from 0.9 to 3.1 s (time to half peak iK,ACh) and from 6.2 to 13.8 s (time to half-deactivation), respectively. In cells transfected with a constitutively active β-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 β-arrestin 2 has the potential to play a major role in desensitization and other aspects of the functioning of the muscarinic K+channel.
Low density lipoproteins induce parasympathetic responsiveness in embryonic chick ventricular myocytes in parallel with a coordinate increase in expression of genes coding for the M2 muscarinic receptor, G alpha i2, and the acetylcholine-sensitive K+ channel.