Crystal Structure of the Mammalian GIRK2 K+ Channel and Gating Regulation by G Proteins, PIP2, and Sodium

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Crystal Structure of the Mammalian GIRK2 K+ Channel and Gating Regulation by G Proteins, PIP2, and Sodium

G protein-gated K(+) channels (Kir3.1-Kir3.4) control electrical excitability in many different cells. Among their functions relevant to human physiology and disease, they regulate the heart rate and govern a wide range of neuronal activities. Here, we present the first crystal structures of a G protein-gated K(+) channel. By comparing the wild-type structure to that of a constitutively active ...

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Quantitative analysis of mammalian GIRK2 channel regulation by G proteins, the signaling lipid PIP2 and Na+ in a reconstituted system

GIRK channels control spike frequency in atrial pacemaker cells and inhibitory potentials in neurons. By directly responding to G proteins, PIP2 and Na(+), GIRK is under the control of multiple signaling pathways. In this study, the mammalian GIRK2 channel has been purified and reconstituted in planar lipid membranes and effects of Gα, Gβγ, PIP2 and Na(+) analyzed. Gβγ and PIP2 must be present ...

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Cooperative regulation by G proteins and Na+ of neuronal GIRK2 K+ channels

G protein gated inward rectifier K(+) (GIRK) channels open and thereby silence cellular electrical activity when inhibitory G protein coupled receptors (GPCRs) are stimulated. Here we describe an assay to measure neuronal GIRK2 activity as a function of membrane-anchored G protein concentration. Using this assay we show that four Gβγ subunits bind cooperatively to open GIRK2, and that intracell...

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The weaver (wv) gene (GIRK2) is a member of the G-protein-gated inwardly rectifying potassium (GIRK) channel family, known effectors in the signal transduction pathway of neurotransmitters such as acetylcholine, dopamine, opioid peptides, and substance P in modulation of neurotransmitter release and neuronal excitability. GIRK2 immunoreactivity is found in but not limited to brain regions known...

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ژورنال

عنوان ژورنال: Cell

سال: 2011

ISSN: 0092-8674

DOI: 10.1016/j.cell.2011.07.046