Control of the cardiac muscarinic K+ channel by beta-arrestin 2.
Control of the cardiac muscarinic K(+) current (i(K,ACh)) by beta-arrestin 2 has been studied. In Chinese hamster ovary cells transfected with m2 muscarinic receptor, muscarinic K(+) channel, receptor kinase (GRK2), and beta-arrestin 2, desensitization of i(K,ACh) during a 3-min application of 10 micrometer 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 beta-arrestin 2 was lost if cells were not co-transfected with GRK2. Resensitization (recovery from desensitization) of i(K,ACh) in cells transfected with beta-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 beta-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 beta-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 beta-arrestin 2 has the potential to play a major role in desensitization and other aspects of the functioning of the muscarinic K(+) channel.
Shui
Z
Z
School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom.
Khan
I A
IA
Haga
T
T
Benovic
J L
JL
Boyett
M R
MR
D000818:Animals; D019390:Arrestins / Q000235:genetics / Q000502:physiology*; D016466:CHO Cells; D006224:Cricetinae; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D051552:beta-Adrenergic Receptor Kinases; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
C000605257:Arrb2 protein, rat; D019390:Arrestins; D015221:Potassium Channels; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D017868:Cyclic AMP-Dependent Protein Kinases; D051552:beta-Adrenergic Receptor Kinases