|
|
|
|
|
|
|
||
The Journal of General Physiology, Vol 98, 517-533, Copyright © 1991 by The Rockefeller University Press
ARTICLES |
H Ito, T Sugimoto, I Kobayashi, K Takahashi, T Katada, M Ui and Y Kurachi
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Using the patch clamp technique, we examined the agonist-free, basal interaction between the muscarinic acetylcholine (m-ACh) receptor and the G protein (GK)-gated muscarinic K+ channel (IK.ACh), and the modification of this interaction by ACh binding to the receptor in single atrial myocytes of guinea pig heart. In the whole cell clamp mode, guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma S) gradually increased the IK.ACh current in the absence of agonists (e.g., acetylcholine). This increase was inhibited in cells that were pretreated with islet-activating protein (IAP, pertussis toxin) or N- ethylmaleimide (NEM). In inside-out patches, even in the absence of agonists, intracellular GTP caused openings of IK.ACh in a concentration-dependent manner in approximately 80% of the patches. Channel activation by GTP in the absence of agonist was much less than that caused by GTP-gamma S. The agonist-independent, GTP-induced activation of IK.ACh was inhibited by the A promoter of IAP (with nicotinamide adenine dinucleotide) or NEM. As the ACh concentration was increased, the GTP-induced maximal open probability of IK.ACh was increased and the GTP concentration for the half-maximal activation of IK.ACh was decreased. Intracellular GDP inhibited the GTP-induced openings of IK.ACh in a concentration-dependent fashion. The half- inhibition of IK.ACh openings occurred at a much lower concentration of GDP in the absence of agonists than in the presence of ACh. From these results, we concluded (a) that the interaction between the m-ACh receptor and GK is essential for basal stimulation of IK.ACh, and (b) that ACh binding to the receptor accelerates the turnover of GK and increases GK's affinity to GTP analogues over GDP.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  E. N. Nikolov and T. T. Ivanova-Nikolova Functional Characterization of a Small Conductance GIRK Channel in Rat Atrial Cells Biophys. J., November 1, 2004; 87(5): 3122 - 3136. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Kurachi and M. Ishii Cell signal control of the G protein-gated potassium channel and its subcellular localization J. Physiol., January 15, 2004; 554(2): 285 - 294. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Sadja, N. Alagem, and E. Reuveny Graded contribution of the Gbeta gamma binding domains to GIRK channel activation PNAS, August 6, 2002; 99(16): 10783 - 10788. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 E. Carmeliet Cardiac Ionic Currents and Acute Ischemia: From Channels to Arrhythmias Physiol Rev, July 1, 1999; 79(3): 917 - 1017. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kawakubo, K. Naruse, T. Matsubara, N. Hotta, and M. Sokabe Characterization of a newly found stretch-activated KCa,ATP channel in cultured chick ventricular myocytes Am J Physiol Heart Circ Physiol, June 1, 1999; 276(6): H1827 - H1838. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kaupmann, V. Schuler, J. Mosbacher, S. Bischoff, H. Bittiger, J. Heid, W. Froestl, S. Leonhard, T. Pfaff, A. Karschin, et al. Human gamma -aminobutyric acid type B receptors are differentially expressed and regulate inwardly rectifying K+ channels PNAS, December 8, 1998; 95(25): 14991 - 14996. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Yamada, A. Inanobe, and Y. Kurachi G Protein Regulation of Potassium Ion Channels Pharmacol. Rev., December 1, 1998; 50(4): 723 - 757. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Otero, L. Xu, Y. Ni, and G. Szabo Receptor-independent Activation of Atrial Muscarinic Potassium Channels in the Absence of Nucleotides J. Biol. Chem., October 30, 1998; 273(44): 28868 - 28872. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Sodickson and B. P. Bean GABAB Receptor-Activated Inwardly Rectifying Potassium Current in Dissociated Hippocampal CA3 Neurons J. Neurosci., October 15, 1996; 16(20): 6374 - 6385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Xu, J. Murphy, and A. d. S. Otero Participation of Nucleoside-diphosphate Kinase in Muscarinic K+ Channel Activation Does Not Involve GTP Formation J. Biol. Chem., August 30, 1996; 271(35): 21120 - 21125. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Krapivinsky, L. Krapivinsky, K. Wickman, and D. E. Clapham Gbeta[IMAGE] Binds Directly to the G Protein-gated K[IMAGE] Channel, I[IMAGE] J. Biol. Chem., December 8, 1995; 270(49): 29059 - 29062. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Krapivinsky, L. Krapivinsky, B. Velimirovic, K. Wickman, B. Navarro, and D. E. Clapham The Cardiac Inward Rectifier K[IMAGE] Channel Subunit, CIR, Does Not Comprise the ATP-sensitive K[IMAGE] Channel, I[IMAGE] J. Biol. Chem., December 1, 1995; 270(48): 28777 - 28779. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Corey and D. E. Clapham The Stoichiometry of Gbeta gamma Binding to G-protein-regulated Inwardly Rectifying K+ Channels (GIRKs) J. Biol. Chem., March 30, 2001; 276(14): 11409 - 11413. [Abstract] [Full Text] [PDF]
|
|
|
|
