%0 Journal Article %1 Hommers2003 %A Hommers, L. G. %A Lohse, M. J. %A Bunemann, M. %D 2003 %J J Biol Chem %K *Potassium Animals CHO Cats Cesium/pharmacology Channels Channels, Channels/chemistry/*physiology Conformation Cricetinae G GTP-Binding Heterotrimeric Humans Inwardly Inwardly-Rectifying Myocardium/metabolism Potassium Protein Protein-Coupled Proteins/*physiology Rectifying Cell %N 2 %P 1037-43 %T Regulation of the inward rectifying properties of G-protein-activated inwardly rectifying K+ (GIRK) channels by Gbeta gamma subunits %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12403784 %V 278 %X Gbetagamma subunits are known to bind to and activate G-protein-activated inwardly rectifying K(+) channels (GIRK) by regulating their open probability and bursting behavior. Studying G-protein regulation of either native GIRK (I(KACh)) channels in feline atrial myocytes or heterologously expressed GIRK1/4 channels in Chinese hamster ovary cells and HEK 293 cells uncovered a novel Gbetagamma subunit mediated regulation of the inwardly rectifying properties of these channels. I(KACh) activated by submaximal concentrations of acetylcholine exhibited a approximately 2.5-fold stronger inward rectification than I(KACh) activated by saturating concentrations of acetylcholine. Similarly, the inward rectification of currents through GIRK1/4 channels expressed in HEK cells was substantially weakened upon maximal stimulation with co-expressed Gbetagamma subunits. Analysis of the outward current block underlying inward rectification demonstrated that the fraction of instantaneously blocked channels was reduced when Gbetagamma was over-expressed. The Gbetagamma induced weakening of inward rectification was associated with reduced potencies for Ba(2+) and Cs(+) to block channels from the extracellular side. Based on these results we propose that saturation of the channel with Gbetagamma leads to a conformational change within the pore of the channel that reduced the potency of extracellular cations to block the pore and increased the fraction of channels inert to a pore block in outward direction.

@article{Hommers2003, abstract = {Gbetagamma subunits are known to bind to and activate G-protein-activated inwardly rectifying K(+) channels (GIRK) by regulating their open probability and bursting behavior. Studying G-protein regulation of either native GIRK (I(KACh)) channels in feline atrial myocytes or heterologously expressed GIRK1/4 channels in Chinese hamster ovary cells and HEK 293 cells uncovered a novel Gbetagamma subunit mediated regulation of the inwardly rectifying properties of these channels. I(KACh) activated by submaximal concentrations of acetylcholine exhibited a approximately 2.5-fold stronger inward rectification than I(KACh) activated by saturating concentrations of acetylcholine. Similarly, the inward rectification of currents through GIRK1/4 channels expressed in HEK cells was substantially weakened upon maximal stimulation with co-expressed Gbetagamma subunits. Analysis of the outward current block underlying inward rectification demonstrated that the fraction of instantaneously blocked channels was reduced when Gbetagamma was over-expressed. The Gbetagamma induced weakening of inward rectification was associated with reduced potencies for Ba(2+) and Cs(+) to block channels from the extracellular side. Based on these results we propose that saturation of the channel with Gbetagamma leads to a conformational change within the pore of the channel that reduced the potency of extracellular cations to block the pore and increased the fraction of channels inert to a pore block in outward direction.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Hommers, L. G. and Lohse, M. J. and Bunemann, M.}, biburl = {https://www.bibsonomy.org/bibtex/2697b94c312aced6b1b46999b11b00e2a/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {940f3383acff49c971137e574850a2b5}, intrahash = {697b94c312aced6b1b46999b11b00e2a}, issn = {0021-9258 (Print) 0021-9258 (Linking)}, journal = {J Biol Chem}, keywords = {*Potassium Animals CHO Cats Cesium/pharmacology Channels Channels, Channels/chemistry/*physiology Conformation Cricetinae G GTP-Binding Heterotrimeric Humans Inwardly Inwardly-Rectifying Myocardium/metabolism Potassium Protein Protein-Coupled Proteins/*physiology Rectifying Cell}, month = {Jan 10}, note = {Hommers, Leif G Lohse, Martin J Bunemann, Moritz Research Support, Non-U.S. Gov't United States The Journal of biological chemistry J Biol Chem. 2003 Jan 10;278(2):1037-43. Epub 2002 Oct 25.}, number = 2, pages = {1037-43}, shorttitle = {Regulation of the inward rectifying properties of G-protein-activated inwardly rectifying K+ (GIRK) channels by Gbeta gamma subunits}, timestamp = {2010-12-14T18:20:39.000+0100}, title = {Regulation of the inward rectifying properties of G-protein-activated inwardly rectifying K+ (GIRK) channels by Gbeta gamma subunits}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12403784}, volume = 278, year = 2003 }