Vol. 50, Issue 4, 723-757, December 1998

G Protein Regulation of Potassium Ion Channels

Mitsuhiko Yamada^a, Atsushi Inanobe and Yoshihisa Kurachi^b

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