ATRIAL G-PROTEIN-ACTIVATED K+-CHANNEL - EXPRESSION CLONING AND MOLECULAR-PROPERTIES

被引:367
作者
DASCAL, N [1 ]
SCHREIBMAYER, W [1 ]
LIM, NF [1 ]
WANG, WZ [1 ]
CHAVKIN, C [1 ]
DIMAGNO, L [1 ]
LABARCA, C [1 ]
KIEFFER, BL [1 ]
GAVERIAUXRUFF, C [1 ]
TROLLINGER, D [1 ]
LESTER, HA [1 ]
DAVIDSON, N [1 ]
机构
[1] CALTECH, DIV BIOL, PASADENA, CA 91125 USA
关键词
D O I
10.1073/pnas.90.21.10235
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:10235 / 10239
页数:5
相关论文
共 46 条
[1]   PHARMACOLOGICALLY DISTINCT ACTIONS OF SEROTONIN ON SINGLE PYRAMIDAL NEURONS OF THE RAT HIPPOCAMPUS RECORDED INVITRO [J].
ANDRADE, R ;
NICOLL, RA .
JOURNAL OF PHYSIOLOGY-LONDON, 1987, 394 :99-124
[2]   A-G PROTEIN COUPLES SEROTONIN AND GABA-B RECEPTORS TO THE SAME CHANNELS IN HIPPOCAMPUS [J].
ANDRADE, R ;
MALENKA, RC ;
NICOLL, RA .
SCIENCE, 1986, 234 (4781) :1261-1265
[3]   REMOVAL OF CA CURRENT INACTIVATION IN DIALYZED GUINEA-PIG ATRIAL CARDIOBALLS BY CA CHELATORS [J].
BECHEM, M ;
POTT, L .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1985, 404 (01) :10-20
[4]   UNCOUPLING OF CARDIAC MUSCARINIC AND BETA-ADRENERGIC RECEPTORS FROM ION CHANNELS BY A GUANINE-NUCLEOTIDE ANALOG [J].
BREITWIESER, GE ;
SZABO, G .
NATURE, 1985, 317 (6037) :538-540
[5]   IONIC CHANNELS AND THEIR REGULATION BY G-PROTEIN SUBUNITS [J].
BROWN, AM ;
BIRNBAUMER, L .
ANNUAL REVIEW OF PHYSIOLOGY, 1990, 52 :197-213
[6]   STRUCTURE AND FUNCTION OF VOLTAGE-SENSITIVE ION CHANNELS [J].
CATTERALL, WA .
SCIENCE, 1988, 242 (4875) :50-61
[7]  
Dale HH, 1914, J PHARMACOL EXP THER, V6, P147
[8]   INVOLVEMENT OF A GTP-BINDING PROTEIN IN MEDIATION OF SEROTONIN AND ACETYLCHOLINE RESPONSES IN XENOPUS OOCYTES INJECTED WITH RAT-BRAIN MESSENGER-RNA [J].
DASCAL, N ;
IFUNE, C ;
HOPKINS, R ;
SNUTCH, TP ;
LUBBERT, H ;
DAVIDSON, N ;
SIMON, MI ;
LESTER, HA .
MOLECULAR BRAIN RESEARCH, 1986, 1 (03) :201-209
[9]   EXPRESSION OF AN ATRIAL G-PROTEIN-ACTIVATED POTASSIUM CHANNEL IN XENOPUS-OOCYTES [J].
DASCAL, N ;
LIM, NF ;
SCHREIBMAYER, W ;
WANG, WZ ;
DAVIDSON, N ;
LESTER, HA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (14) :6596-6600
[10]  
DASCAL N, 1992, METHODS MOL BIOL PRO, V13