Atrial G Protein-activated K+ Channel: Expression Cloning and Molecular Properties

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1993 Nov 1

PMID 8234283

Citations 90

Authors

N Dascal

W Schreibmayer

N F Lim

W Wang

C Chavkin

L DiMagno

C Labarca

B L Kieffer

C Gaveriaux-Ruff

D Trollinger

Affiliations

Soon will be listed here.

Abstract

Activity of several ion channels is controlled by heterotrimeric GTP-binding proteins (G proteins) via a membrane-delimited pathway that does not involve cytoplasmic intermediates. The best studied example is the K+ channel activated by muscarinic agonists in the atrium, which plays a crucial role in regulating the heartbeat. To enable studies of the molecular mechanisms of activation, this channel, denoted KGA, was cloned from a rat atrium cDNA library by functional coupling to coexpressed serotonin type 1A receptors in Xenopus oocytes. KGA displays regions of sequence homology to other inwardly rectifying channels as well as unique regions that may govern G-protein interaction. The expressed KGA channel is activated by serotonin 1A, muscarinic m2, and delta-opioid receptors via G proteins. KGA is activated by guanosine 5'-[gamma-thio]triphosphate in excised patches, confirming activation by a membrane-delimited pathway, and displays a conductance equal to that of the endogenous channel in atrial cells. The hypothesis that similar channels play a role in neuronal inhibition is supported by the cloning of a nearly identical channel (KGB1) from a rat brain cDNA library.

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References

Yatani A, CODINA J, Brown A, Birnbaumer L . Direct activation of mammalian atrial muscarinic potassium channels by GTP regulatory protein Gk. Science. 1987; 235(4785):207-11. DOI: 10.1126/science.2432660. View

Hamill O, Marty A, Neher E, Sakmann B, Sigworth F . Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981; 391(2):85-100. DOI: 10.1007/BF00656997. View

Hammer R, Berrie C, Birdsall N, BURGEN A, Hulme E . Pirenzepine distinguishes between different subclasses of muscarinic receptors. Nature. 1980; 283(5742):90-2. DOI: 10.1038/283090a0. View

Ruoslahti E . Integrins. J Clin Invest. 1991; 87(1):1-5. PMC: 294975. DOI: 10.1172/JCI114957. View

Logothetis D, Kurachi Y, Galper J, Neer E, Clapham D . The beta gamma subunits of GTP-binding proteins activate the muscarinic K+ channel in heart. Nature. 1987; 325(6102):321-6. DOI: 10.1038/325321a0. View

Kim D . Modulation of acetylcholine-activated K+ channel function in rat atrial cells by phosphorylation. J Physiol. 1991; 437:133-55. PMC: 1180040. DOI: 10.1113/jphysiol.1991.sp018588. View

Hoyer D, Schoeffter P . 5-HT receptors: subtypes and second messengers. J Recept Res. 1991; 11(1-4):197-214. DOI: 10.3109/10799899109066399. View

KYTE J, Doolittle R . A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982; 157(1):105-32. DOI: 10.1016/0022-2836(82)90515-0. View

Kennelly P, KREBS E . Consensus sequences as substrate specificity determinants for protein kinases and protein phosphatases. J Biol Chem. 1991; 266(24):15555-8. View

10.

Brown A, Birnbaumer L . Ionic channels and their regulation by G protein subunits. Annu Rev Physiol. 1990; 52:197-213. DOI: 10.1146/annurev.ph.52.030190.001213. View

11.

Dascal N, Lim N, Schreibmayer W, Wang W, Davidson N, Lester H . Expression of an atrial G-protein-activated potassium channel in Xenopus oocytes. Proc Natl Acad Sci U S A. 1993; 90(14):6596-600. PMC: 46979. DOI: 10.1073/pnas.90.14.6596. View

12.

Bechem M, Pott L . Removal of Ca current inactivation in dialysed guinea-pig atrial cardioballs by Ca chelators. Pflugers Arch. 1985; 404(1):10-20. DOI: 10.1007/BF00581485. View

13.

Karschin A, Ho B, Labarca C, Elroy-Stein O, Moss B, Davidson N . Heterologously expressed serotonin 1A receptors couple to muscarinic K+ channels in heart. Proc Natl Acad Sci U S A. 1991; 88(13):5694-8. PMC: 51944. DOI: 10.1073/pnas.88.13.5694. View

14.

Breitwieser G, Szabo G . Uncoupling of cardiac muscarinic and beta-adrenergic receptors from ion channels by a guanine nucleotide analogue. Nature. 1985; 317(6037):538-40. DOI: 10.1038/317538a0. View

15.

Edwards C, KUFFLER S, TRAUTWEIN W . Changes in membrane characteristics of heart muscle during inhibition. J Gen Physiol. 1956; 40(1):135-45. PMC: 2147603. DOI: 10.1085/jgp.40.1.135. View

16.

Kurachi Y, Tung R, Ito H, Nakajima T . G protein activation of cardiac muscarinic K+ channels. Prog Neurobiol. 1992; 39(3):229-46. DOI: 10.1016/0301-0082(92)90017-9. View

17.

Peralta E, Ashkenazi A, Winslow J, Smith D, Ramachandran J, Capon D . Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors. EMBO J. 1987; 6(13):3923-9. PMC: 553870. DOI: 10.1002/j.1460-2075.1987.tb02733.x. View

18.

Kubo Y, Baldwin T, Jan Y, Jan L . Primary structure and functional expression of a mouse inward rectifier potassium channel. Nature. 1993; 362(6416):127-33. DOI: 10.1038/362127a0. View

19.

Kurachi Y, Ito H, Sugimoto T . Positive cooperativity in activation of the cardiac muscarinic K+ channel by intracellular GTP. Pflugers Arch. 1990; 416(1-2):216-8. DOI: 10.1007/BF00370247. View

20.

Kurachi Y, Nakajima T, Sugimoto T . Short-term desensitization of muscarinic K+ channel current in isolated atrial myocytes and possible role of GTP-binding proteins. Pflugers Arch. 1987; 410(3):227-33. DOI: 10.1007/BF00580270. View