Atrial G protein-activated K+ channel: expression cloning and molecular properties.
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.
Dascal
N
N
Division of Biology, California Institute of Technology, Pasadena 91125.
Schreibmayer
W
W
Lim
N F
NF
Wang
W
W
Chavkin
C
C
DiMagno
L
L
Labarca
C
C
Kieffer
B L
BL
Gaveriaux-Ruff
C
C
Trollinger
D
D
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000378:metabolism; D005071:Evoked Potentials / Q000187:drug effects; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D019204:GTP-Binding Proteins / Q000378:metabolism*; D015870:Gene Expression; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006325:Heart Atria; D008564:Membrane Potentials / Q000187:drug effects; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015221:Potassium Channels / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D011976:Receptors, Muscarinic / Q000502:physiology; D017465:Receptors, Opioid, delta / Q000502:physiology; D011985:Receptors, Serotonin / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D012701:Serotonin / Q000494:pharmacology; D014981:Xenopus
D018076:DNA, Complementary; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C497068:Kcnj3 protein, rat; D015221:Potassium Channels; D011976:Receptors, Muscarinic; D017465:Receptors, Opioid, delta; D011985:Receptors, Serotonin; D012701:Serotonin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D002217:Carbachol; D019204:GTP-Binding Proteins