Functional characterization and localization of a cardiac-type inwardly rectifying K+ channel.
We cloned inwardly rectifying K+ channel cDNAs from porcine, rat and human, which were structurally almost identical with recently reported CIR(cKATP-1). The expression of CIR alone was low and unstable in Xenopus oocytes. The CIR/GIRK1 co-expression showed an increased current amplitude. Both the CIR and CIR/GIRK1 currents increased by coexpressing G beta gamma. The CIR and CIR/GIRK1 currents displayed two qualitative differences. (1) The conductance of the CIR channel did not saturate, but that of the CIR/GIRK1 channel showed saturation at hyperpolarized potential. (2) The CIR current showed instantaneous activation upon hyperpolarization, whereas the CIR/GIRK1 current exhibited slow activation, which was fitted by the sum of two exponentials. The CIR/GIRK1 current was also different from the GIRK1 current. The activation of the CIR/GIRK1 current was approximately ten times faster than that of the GIRK1 current. The increase in current amplitude and the qualitative differences imply the formation of functional heteromultimer. The CIR/GIRK1 channel showed differences from the native muscarinic K+ channel in that the basal level before m2 receptor activation is significantly large, and that the activation kinetics are much faster. Using anti-CIR antiserum, the CIR was detected in myocardial cells of the atrium and the ventricular subendocardial layer, and in the cardiac ganglion.
Iizuka
M
M
Department of Molecular and Cellular Biology, Nippon Boehringer Ingelheim Co, Ltd, Japan.
Kubo
Y
Y
Tsunenari
I
I
Pan
C X
CX
Akiba
I
I
Kono
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary; D006801:Humans; D007150:Immunohistochemistry; D007700:Kinetics; D008564:Membrane Potentials; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D015221:Potassium Channels