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Activation of the cloned muscarinic potassium channel by G protein βγ subunits

Abstract

ACETYLCHOLINE released during parasv mpathetic stimulation of the vagal nerve slows the heart rate through the activation of muscarinic receptors and subsequent opening of an inwardly rectifying potassium channel1. The activation of these muscarinic potassium channels is mediated by a pertussis toxin-sensitive heterotrimeric GTP-binding protein (G protein)2,3. It has not been resolved whether exogenously applied Gα4,5 or Gβγ6,7, or both, activate the channel. Using a heterologous expression system, we have tested the ability of different G protein subunits to activate the cloned muscarinic potassium channel, GIRK18,9. We report here that coexpression of GIRK1 with Gβγ but not Gαβγ in Xenopus oocytes results in channel activity that persists in the absence of cytoplasmic GTP. This activity is reduced by fusion proteins of the (β-adrenergic receptor kinase and of recombinant Gαi–GDP, both of which are known to interact with Gβγ10,11. Moreover, application of recombinant Gβγ, but not Gαi–GTP-γS, activates GIRK1 channels. Thus Gβγ appears to be sufficient for the activation of GIRK1 muscarinic potassium channels.

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Reuveny, E., Slesinger, P., Inglese, J. et al. Activation of the cloned muscarinic potassium channel by G protein βγ subunits. Nature 370, 143–146 (1994). https://doi.org/10.1038/370143a0

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