A fundamental role for KChIPs in determining the molecular properties and trafficking of Kv4.2 potassium channels

Riichi Shibata, Hiroaki Misonou, Claire R. Campomanes, Anne E. Anderson, Laura A. Schrader, Lisa C. Doliveira, Karen I. Carroll, J. David Sweatt, Kenneth J. Rhodes, James Trimmer

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211 Citations (Scopus)

Abstract

Kv4 potassium channels regulate action potentials in neurons and cardiac myocytes. Co-expression of EF hand-containing Ca2+-binding proteins termed KChIPs with pore-forming Kv4 α subunits causes changes in the gating and amplitude of Kv4 currents (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). Here we show that KChIPs profoundly affect the intracellular trafficking and molecular properties of Kv4.2 α subunits. Coexpression of KChIPs1-3 causes a dramatic redistribution of Kv4.2, releasing intrinsic endoplasmic reticulum retention and allowing for trafficking to the cell surface. KChIP co-expression also causes fundamental changes in Kv4.2 steady-state expression levels, phosphorylation, detergent solubility, and stability that reconstitute the molecular properties of Kv4.2 in native cells. Interestingly, the KChIP4a isoform, which exhibits unique effects on Kv4 channel gating, does not exert these effects on Kv4.2 and negatively influences the impact of other KChIPs. We provide evidence that these KChIP effects occur through the masking of an N-terminal Kv4.2 hydrophobic domain. These studies point to an essential role for KChIPs in determining both the biophysical and molecular characteristics of Kv4 channels and provide a molecular basis for the dramatic phenotype of KChIP knockout mice.

Original languageEnglish (US)
Pages (from-to)36445-36454
Number of pages10
JournalJournal of Biological Chemistry
Volume278
Issue number38
DOIs
StatePublished - Sep 19 2003

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Shal Potassium Channels
Phosphorylation
Detergents
Neurons
Carrier Proteins
Protein Isoforms
Solubility
EF Hand Motifs
Cardiac Myocytes
Knockout Mice
Endoplasmic Reticulum
Action Potentials
Phenotype

ASJC Scopus subject areas

  • Biochemistry

Cite this

Shibata, R., Misonou, H., Campomanes, C. R., Anderson, A. E., Schrader, L. A., Doliveira, L. C., ... Trimmer, J. (2003). A fundamental role for KChIPs in determining the molecular properties and trafficking of Kv4.2 potassium channels. Journal of Biological Chemistry, 278(38), 36445-36454. https://doi.org/10.1074/jbc.M306142200

A fundamental role for KChIPs in determining the molecular properties and trafficking of Kv4.2 potassium channels. / Shibata, Riichi; Misonou, Hiroaki; Campomanes, Claire R.; Anderson, Anne E.; Schrader, Laura A.; Doliveira, Lisa C.; Carroll, Karen I.; Sweatt, J. David; Rhodes, Kenneth J.; Trimmer, James.

In: Journal of Biological Chemistry, Vol. 278, No. 38, 19.09.2003, p. 36445-36454.

Research output: Contribution to journalArticle

Shibata, R, Misonou, H, Campomanes, CR, Anderson, AE, Schrader, LA, Doliveira, LC, Carroll, KI, Sweatt, JD, Rhodes, KJ & Trimmer, J 2003, 'A fundamental role for KChIPs in determining the molecular properties and trafficking of Kv4.2 potassium channels', Journal of Biological Chemistry, vol. 278, no. 38, pp. 36445-36454. https://doi.org/10.1074/jbc.M306142200
Shibata, Riichi ; Misonou, Hiroaki ; Campomanes, Claire R. ; Anderson, Anne E. ; Schrader, Laura A. ; Doliveira, Lisa C. ; Carroll, Karen I. ; Sweatt, J. David ; Rhodes, Kenneth J. ; Trimmer, James. / A fundamental role for KChIPs in determining the molecular properties and trafficking of Kv4.2 potassium channels. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 38. pp. 36445-36454.
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AU - Schrader, Laura A.

AU - Doliveira, Lisa C.

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