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Vol. 50, Issue 4, 723-757, December 1998
Department of Pharmacology II, Faculty of Medicine, Osaka
University, Osaka, Japan
I. Introduction
II. Functional Analysis of G Protein-Mediated Activation of
Muscarinic K+ Channels in Cardiac Atrial Myocytes
A. Time-Dependent Response of the Whole-Cell Muscarinic
K+ Current to Acetylcholine
1. The G protein cyclic reaction mediating the receptor-to-channel
signal transmission.
2. Activation phase.
3. The phase of short-term desensitization.
4. Deactivation of the response of the muscarinic K+
channel.
B. Quantitative Analysis of G Protein-Mediated Activation of the
Muscarinic K+ Channel
1. Single-channel characteristics of the muscarinic K+
channel.
2. Positive cooperative effect of GTP on muscarinic K+
channel activity.
3. Spectral analysis of the muscarinic K+ channel
currents in the presence of different concentrations of intracellular
GTP.
4. A possible mechanism for the G protein-mediated increase in the
functional numbers of muscarinic K+ channels.
C. Modulation of G Protein-Mediated Activation of the Muscarinic
K+ Channel
III. Molecular Analysis of G Protein-Gated K+ Channels
A. Cloning of Inwardly Rectifying K+ Channels
B. Subunits of G Protein-Gated K+ Channels
C. Tissue Distribution of GIRK Subunits
1. Peripheral tissues.
2. Central nervous system.
D. Expression of G Protein-Gated K+ Channels
E. Tetrameric Structure
F. Molecular Mechanism Underlying G Protein Activation of G
Protein-Gated K+ Channels
1. Interaction between G protein 
subunits and subunits of G
protein-gated K+ channels.
2. Mechanism underlying G protein subunitinduced
activation of G protein-gated K+ channels.
3. Interaction between subunits of G protein-gated K+
channels, G
proteins, and membrane agonist
receptors.
4. Possible mechanisms underlying specific signal transduction in
the receptor/G protein/G protein-gated K+ channel
system.
IV. Voltage-Dependent Properties of G Protein-Gated K+
Channels
A. Inwardly-Rectifying K+ Channels
1. Voltage-dependent change in inwardly rectifying K+
channel activity.
2. Mg2+ and polyamine block.
3. Mg2+/polyamine block sites in the inwardly
rectifying K+ channel pore.
B. Inward Rectification of G Protein-Gated K+ Channels
1. Inward rectification of the muscarinic K+
channel.
2. Mg2+/polyamine block of G protein-gated
K+ channels.
3. The Mg2+/polyamine-binding sites in G protein-gated
K+ channels.
4. Slow relaxation of G protein-gated K+ channels
containing GIRK1.
V. Pharmacological Properties of G Protein-Gated K+
Channels
VI. Localization of the G Protein-Gated K+ Channel in
Different Organs
A. Cardiac Atrial Myocytes
B. Neurons
1. Differential cellular and subcellular distribution of GIRK
subunits.
2. Functional significance of differential subcellular distribution
of GIRK subunits.
C. Endocrine Cells
VII. Weaver Mutant Mice and the GIRK2 Gene
VIII. Conclusions
Acknowledgments
References
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A. Inanobe, S. Fujita, Y. Makino, K. Matsushita, M. Ishii, M. Chachin, and Y. Kurachi Interaction between the RGS domain of RGS4 with G protein {alpha} subunits mediates the voltage-dependent relaxation of the G protein-gated potassium channel J. Physiol., August 15, 2001; 535(1): 133 - 143. [Abstract] [Full Text] [PDF]
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J. L Leaney, L. V Dekker, and A. Tinker Regulation of a G protein-gated inwardly rectifying K+ channel by a Ca2+-independent protein kinase C J. Physiol., July 15, 2001; 534(2): 367 - 379. [Abstract] [Full Text] [PDF]
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P. A Smith, L. A Sellers, and P. P A Humphrey Somatostatin activates two types of inwardly rectifying K+ channels in MIN-6 cells J. Physiol., April 1, 2001; 532(1): 127 - 142. [Abstract] [Full Text] [PDF]
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Q.-Q. Sun, J. R Huguenard, and D. A Prince Neuropeptide Y receptors differentially modulate G-protein-activated inwardly rectifying K+ channels and high-voltage-activated Ca2+ channels in rat thalamic neurons J. Physiol., February 15, 2001; 531(1): 67 - 79. [Abstract] [Full Text] [PDF]
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D. Wang and D. L Armstrong Tetraethylammonium potentiates the activity of muscarinic potassium channels in guinea-pig atrial myocytes J. Physiol., December 15, 2000; 529(3): 699 - 705. [Abstract] [Full Text] [PDF]
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D. Dobrev, E. Wettwer, H. M. Himmel, A. Kortner, E. Kuhlisch, S. Schuler, W. Siffert, and U. Ravens G-Protein {beta}3-Subunit 825T Allele Is Associated With Enhanced Human Atrial Inward Rectifier Potassium Currents Circulation, August 8, 2000; 102(6): 692 - 697. [Abstract] [Full Text] [PDF]
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H. M. Himmel, D. Meyer zu Heringdorf, E. Graf, D. Dobrev, A. Kortner, S. Schüler, K. H. Jakobs, and U. Ravens Evidence for Edg-3 Receptor-Mediated Activation of IK.ACh by Sphingosine-1-Phosphate in Human Atrial Cardiomyocytes Mol. Pharmacol., August 1, 2000; 58(2): 449 - 454. [Abstract] [Full Text]
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S. Fujita, A. Inanobe, M. Chachin, Y. Aizawa, and Y. Kurachi A regulator of G protein signalling (RGS) protein confers agonist-dependent relaxation gating to a G protein-gated K+ channel J. Physiol., July 15, 2000; 526(2): 341 - 347. [Abstract] [Full Text] [PDF]
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D. Yakubovich, V. Pastushenko, A. Bitler, C. W Dessauer, and N. Dascal Slow modal gating of single G protein-activated K+ channels expressed in Xenopus oocytes J. Physiol., May 1, 2000; 524(3): 737 - 755. [Abstract] [Full Text] [PDF]
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H. Kitamura, M. Yokoyama, H. Akita, K. Matsushita, Y. Kurachi, and M. Yamada Tertiapin Potently and Selectively Blocks Muscarinic K+ Channels in Rabbit Cardiac Myocytes J. Pharmacol. Exp. Ther., April 1, 2000; 293(1): 196 - 205. [Abstract] [Full Text]
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 M.-C. Wellner-Kienitz, K. Bender, T. Meyer, M. Bunemann, and L. Pott Overexpressed A1 Adenosine Receptors Reduce Activation of Acetylcholine-Sensitive K+ Current by Native Muscarinic M2 Receptors in Rat Atrial Myocytes Circ. Res., March 31, 2000; 86(6): 643 - 648. [Abstract] [Full Text] [PDF]
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V. Ruiz-Velasco and S. R. Ikeda Multiple G-Protein beta gamma Combinations Produce Voltage-Dependent Inhibition of N-Type Calcium Channels in Rat Superior Cervical Ganglion Neurons J. Neurosci., March 15, 2000; 20(6): 2183 - 2191. [Abstract] [Full Text] [PDF]
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D. Vorobiov, A. K. Bera, T. Keren-Raifman, R. Barzilai, and N. Dascal Coupling of the Muscarinic m2 Receptor to G Protein-activated K+ Channels via Galpha z and a Receptor-Galpha z Fusion Protein. FUSION BETWEEN THE RECEPTOR AND Galpha z ELIMINATES CATALYTIC (COLLISION) COUPLING J. Biol. Chem., February 11, 2000; 275(6): 4166 - 4170. [Abstract] [Full Text] [PDF]
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J. L. Leaney, G. Milligan, and A. Tinker The G Protein alpha Subunit Has a Key Role in Determining the Specificity of Coupling to, but Not the Activation of, G Protein-gated Inwardly Rectifying K+ Channels J. Biol. Chem., January 14, 2000; 275(2): 921 - 929. [Abstract] [Full Text] [PDF]
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T. Rohacs, J. Chen, G. D. Prestwich, and D. E. Logothetis Distinct Specificities of Inwardly Rectifying K+ Channels for Phosphoinositides J. Biol. Chem., December 17, 1999; 274(51): 36065 - 36072. [Abstract] [Full Text] [PDF]
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 O.-E. Brodde and M. C. Michel Adrenergic and Muscarinic Receptors in the Human Heart Pharmacol. Rev., December 1, 1999; 51(4): 651 - 690. [Abstract] [Full Text] [PDF]
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A. Inanobe, Y. Horio, A. Fujita, M. Tanemoto, H. Hibino, K. Inageda, and Y. Kurachi Molecular cloning and characterization of a novel splicing variant of the Kir3.2 subunit predominantly expressed in mouse testis J. Physiol., November 15, 1999; 521(1): 19 - 30. [Abstract] [Full Text] [PDF]
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T. Takigawa and C. Alzheimer Variance Analysis of Current Fluctuations of Adenosine- and Baclofen-Activated GIRK Channels in Dissociated Neocortical Pyramidal Cells J Neurophysiol, September 1, 1999; 82(3): 1647 - 1650. [Abstract] [Full Text] [PDF]
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T. Tsunenari, T. Kurahashi, and A. Kaneko Activation by bitter substances of a cationic channel in membrane patches excised from the bullfrog taste receptor cell J. Physiol., September 1, 1999; 519(2): 397 - 404. [Abstract] [Full Text] [PDF]
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T. Takigawa and C. Alzheimer G protein-activated inwardly rectifying K+ (GIRK) currents in dendrites of rat neocortical pyramidal cells J. Physiol., June 1, 1999; 517(2): 385 - 390. [Abstract] [Full Text] [PDF]
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M. Bunemann and M M. Hosey G-protein coupled receptor kinases as modulators of G-protein signalling J. Physiol., May 15, 1999; 517(1): 5 - 23. [Abstract] [Full Text] [PDF]
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T. Meyer, M.-C. Wellner-Kienitz, A. Biewald, K. Bender, A. Eickel, and L. Pott Depletion of Phosphatidylinositol 4,5-Bisphosphate by Activation of Phospholipase C-coupled Receptors Causes Slow Inhibition but Not Desensitization of G Protein-gated Inward Rectifier K+ Current in Atrial Myocytes J. Biol. Chem., February 16, 2001; 276(8): 5650 - 5658. [Abstract] [Full Text] [PDF]
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K. Bender, M.-C. Wellner-Kienitz, A. Inanobe, T. Meyer, Y. Kurachi, and L. Pott Overexpression of Monomeric and Multimeric GIRK4 Subunits in Rat Atrial Myocytes Removes Fast Desensitization and Reduces Inward Rectification of Muscarinic K+ Current (IK(ACh)). EVIDENCE FOR FUNCTIONAL HOMOMERIC GIRK4 CHANNELS J. Biol. Chem., July 27, 2001; 276(31): 28873 - 28880. [Abstract] [Full Text] [PDF]
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M.-C. Wellner-Kienitz, K. Bender, and L. Pott Overexpression of beta 1 and beta 2 Adrenergic Receptors in Rat Atrial Myocytes. DIFFERENTIAL COUPLING TO G PROTEIN-GATED INWARD RECTIFIER K+ CHANNELS VIA Gs AND Gi/o J. Biol. Chem., September 28, 2001; 276(40): 37347 - 37354. [Abstract] [Full Text] [PDF]
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M. Ishii, A. Inanobe, and Y. Kurachi PIP3 inhibition of RGS protein and its reversal by Ca2+/calmodulin mediate voltage-dependent control of the G protein cycle in a cardiac K+ channel PNAS, April 2, 2002; 99(7): 4325 - 4330. [Abstract] [Full Text] [PDF]
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J. L. Leaney and A. Tinker The role of members of the pertussis toxin-sensitive family of G proteins in coupling receptors to the activation of the G protein-gated inwardly rectifying potassium channel PNAS, May 9, 2000; 97(10): 5651 - 5656. [Abstract] [Full Text] [PDF]
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M. Ishii, A. Inanobe, S. Fujita, Y. Makino, Y. Hosoya, and Y. Kurachi Ca2+ Elevation Evoked by Membrane Depolarization Regulates G Protein Cycle via RGS Proteins in the Heart Circ. Res., November 23, 2001; 89(11): 1045 - 1050. [Abstract] [Full Text] [PDF]
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