Regulation of the inward rectifying properties of G-protein-activated
inwardly rectifying K+ (GIRK) channels by Gbeta gamma subunits
L. Hommers, M. Lohse, und M. Bunemann. J Biol Chem, 278 (2):
1037-43(Januar 2003)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..
Zusammenfassung
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.
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.
%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
}