Conserved Kv4 N-terminal domain critical for effects of Kv channel-interacting protein 2.2 on channel expression and gating.
Association of Kv channel-interacting proteins (KChIPs) with Kv4 channels leads to modulation of these A-type potassium channels (An, W. F., Bowlby, M. R., Betty, M., Cao, J., Ling, H. P., Mendoza, G., Hinson, J. W., Mattsson, K. I., Strassle, B. W., Trimmer, J. S., and Rhodes, K. J. (2000) Nature 403, 553-556). We cloned a KChIP2 splice variant (KChIP2.2) from human ventricle. In comparison with KChIP2.1, coexpression of KChIP2.2 with human Kv4 channels in mammalian cells slowed the onset of Kv4 current inactivation (2-3-fold), accelerated the recovery from inactivation (5-7-fold), and shifted Kv4 steady-state inactivation curves by 8-29 mV to more positive potentials. The features of Kv4.2/KChIP2.2 currents closely resemble those of cardiac rapidly inactivating transient outward currents. KChIP2.2 stimulated the Kv4 current density in Chinese hamster ovary cells by approximately 55-fold. This correlated with a redistribution of immunoreactivity from perinuclear areas to the plasma membrane. Increased Kv4 cell-surface expression and current density were also obtained in the absence of KChIP2.2 when the highly conserved proximal Kv4 N terminus was deleted. The same domain is required for association of KChIP2.2 with Kv4 alpha-subunits. We propose that an efficient transport of Kv4 channels to the cell surface depends on KChIP binding to the Kv4 N-terminal domain. Our data suggest that the binding is necessary, but not sufficient, for the functional activity of KChIPs.
Bähring
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R
Institut für Neurale Signalverarbeitung, Zentrum für Molekulare Neurobiologie, Universität Hamburg, Martinistrasse 52, 20246 Hamburg, Germany.
Dannenberg
J
J
Peters
H C
HC
Leicher
T
T
Pongs
O
O
Isbrandt
D
D
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002135:Calcium-Binding Proteins / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology*; D002460:Cell Line; D003001:Cloning, Molecular; D017124:Conserved Sequence; D006224:Cricetinae; D004553:Electric Conductivity; D006801:Humans; D015640:Ion Channel Gating; D051605:Kv Channel-Interacting Proteins; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D051672:Shal Potassium Channels
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; C496752:KCNIP2 protein, human; D051605:Kv Channel-Interacting Proteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051672:Shal Potassium Channels