DOI: 10.1073/pnas.221168498. A role for frequenin, a Ca <sup>2+</sup> -binding protein, as a regulator of Kv4 K <sup>+</sup> -currents

A role for frequenin, a Ca 2+ -binding protein, as a regulator of Kv4 K + -currents

10.1073/pnas.221168498

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Frequenin, a Ca 2+ -binding protein, has previously been implicated in the regulation of neurotransmission, possibly by affecting ion channel function. Here, we provide direct evidence that frequenin is a potent and specific modulator of Kv4 channels, the principal molecular components of subthreshold activating A-type K + currents. Frequenin increases Kv4.2 current amplitudes (partly by enhancing surface expression of Kv4.2 proteins) and it slows the inactivation time course in a Ca 2+ -dependent manner. It also accelerates recovery from inactivation. Closely related Ca 2+ -binding proteins, such as neurocalcin and visinin-like protein (VILIP)-1 have no such effects. Specificity for Kv4 currents is suggested because frequenin does not modulate Kv1.4 or Kv3.4 currents. Frequenin has negligible effects on Kv4.1 current inactivation time course. By using chimeras made from Kv4.2 and Kv4.1 subunits, we determined that the differential effects of frequenin are mediated by means of the Kv4 N terminus. Immunohistochemical analysis demonstrates that frequenin and Kv4.2 channel proteins are coexpressed in similar neuronal populations and have overlapping subcellular localizations in brain. Coimmunoprecipitation experiments demonstrate that a physical interaction occurs between these two proteins in brain membranes. Together, our data provide strong support for the concept that frequenin may be an important Ca 2+ -sensitive regulatory component of native A-type K + currents.

Bibliography

Nakamura, T. Y., Pountney, D. J., Ozaita, A., Nandi, S., Ueda, S., Rudy, B., & Coetzee, W. A. (2001). A role for frequenin, a Ca 2+ -binding protein, as a regulator of Kv4 K + -currents. Proceedings of the National Academy of Sciences, 98(22), 12808â12813.

Authors 7

Tomoe Y. Nakamura (first)
David J. Pountney (additional)
Ander Ozaita (additional)
Sumon Nandi (additional)
Stefanie Ueda (additional)
Bernardo Rudy (additional)
William A. Coetzee (additional)

References 42 Referenced 114

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:34 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 9 a.m.)
Indexed	3 months, 3 weeks ago (May 2, 2025, 5 a.m.)
Issued	23 years, 10 months ago (Oct. 16, 2001)
Published	23 years, 10 months ago (Oct. 16, 2001)
Published Online	23 years, 10 months ago (Oct. 16, 2001)
Published Print	23 years, 10 months ago (Oct. 23, 2001)

Funders 0

None

BibTeX

@article{Nakamura_2001, title={A role for frequenin, a Ca 2+ -binding protein, as a regulator of Kv4 K + -currents}, volume={98}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.221168498}, DOI={10.1073/pnas.221168498}, number={22}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Nakamura, Tomoe Y. and Pountney, David J. and Ozaita, Ander and Nandi, Sumon and Ueda, Stefanie and Rudy, Bernardo and Coetzee, William A.}, year={2001}, month=oct, pages={12808–12813} }

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