Arrival of agonist is generally thought to initiate the signal transduction process in G protein-receptor coupled systems. However, the muscarinic atrial K+ (K+[ACh]) channel opens spontaneously in the absence of applied agonist, giving a noisy appearance to the current records. We investigated the nature and origin of the noise by measuring single channel currents in cell-attached or excised, inside-out membrane patches. Guanosine triphosphate (GTP) produced identical single channel currents in a concentration- and Mg(2+)-dependent manner in the presence or absence of carbachol, but the requirements for GTP were greater in the absence of agonist. Hence the agonist-independent currents appeared to be produced by an endogenous G protein, Gk. This prediction was confirmed when an affinity-purified, sequence-specific Gi-3 alpha antibody or pertussis toxin (PTX) blocked the agonist-independent currents. Candidate endogenous agonists were ruled out by the lack of effect of their corresponding antagonists. Thus agonist-independent currents had the same nature as agonist-dependent K+[ACh] currents and seemed to originate in the same way. We have developed a hypothesis in which agonist-free, empty receptors prime Gk with GTP and Gk activates atrial K+ [ACh] channels producing basal currents or noise. Agonist-independent activation by G proteins of effectors including ion channels appears to be a common occurrence.
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1 June 1991
Article|
June 01 1991
The nature and origin of spontaneous noise in G protein-gated ion channels.
K Okabe,
K Okabe
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030.
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A Yatani,
A Yatani
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030.
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A M Brown
A M Brown
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030.
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K Okabe
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030.
A Yatani
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030.
A M Brown
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030.
Online ISSN: 1540-7748
Print ISSN: 0022-1295
J Gen Physiol (1991) 97 (6): 1279–1293.
Citation
K Okabe, A Yatani, A M Brown; The nature and origin of spontaneous noise in G protein-gated ion channels.. J Gen Physiol 1 June 1991; 97 (6): 1279–1293. doi: https://doi.org/10.1085/jgp.97.6.1279
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