title: Receptor-independent activation of atrial muscarinic potassium channels in the absence of nucleotides.
abstract: The removal of nucleotides from the solution bathing the inner face of excised patches of frog atrial membranes was found to activate muscarinic K+ channels in the absence of agonists. Channel activation was also observed in Mg2+-free solutions and blocked by low (0.1-10 microM) concentrations of GDP or GTP. After full activation was achieved, channel openings were abolished by the application of GDP-bound Galphai2 but were not affected by exogenous Gbetagamma dimers, suggesting that effector activation is a consequence of the liberation of betagamma subunits from endogenous G proteins. The process of channel activation in the absence of nucleotides seems to be receptor-independent, because it is not influenced by muscarinic receptor agonists and antagonists or by treatment with uncoupling agents such as pertussis toxin or N-ethyl maleimide. Taken together, these results suggest that the loss of GDP from the G protein nucleotide binding site promotes its uncoupling from receptors and destabilizes the Galpha(empty)betagamma heterotrimer. Therefore, the nucleotide-free form of G proteins has some of the characteristics of the GTP-bound, activated form.
authors.affiliation: Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia 22906-0011, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Otero
authors.forename: L
authors.initials: L
authors.lastname: Xu
authors.forename: Y
authors.initials: Y
authors.lastname: Ni
authors.forename: G
authors.initials: G
authors.lastname: Szabo
mesh_terms: D000818:Animals; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism*; D015640:Ion Channel Gating; D018721:Muscarinic Agonists / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D011892:Rana catesbeiana; D011976:Receptors, Muscarinic / Q000378:metabolism*
chemical_list: D018721:Muscarinic Agonists; D015221:Potassium Channels; D011976:Receptors, Muscarinic; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate