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Molecular and functional characterization of Kv4.2 and KChIP2 expressed in the porcine left ventricle

  • Cardiovascular System
  • Published:
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Abstract

Recent studies showed that the Ca2+-independent transient outward current (I to) is very small or even not detectable in the porcine left ventricle. We investigated whether an altered molecular expression or function of voltage-dependent potassium channels belonging to the Kv4 sub-family and their ancillary Ca2+-binding β sub-unit KChIP2, which contribute to the major fraction of I to in other species, may underlie this lack of a significant I to in the porcine left ventricle. RT-PCR analysis with degenerate primers showed that both Kv4 mRNA and KChIP2 mRNA are expressed in porcine left ventricular tissue and in isolated ventricular myocytes. PCR cloning and sequence analysis predicted proteins with >98% identity to rat and human Kv4.2 and >99% identity to rat and human KChIP2. Heterologous expression of porcine Kv4.2 in Xenopus laevis oocytes gave rise to currents with characteristic properties of rat and human Kv4.2, and co-expression with its KChIP2 sub-unit increased current density (tenfold), slowed inactivation (twofold) and accelerated recovery from inactivation (tenfold). Kv4.2 immunohistochemistry in porcine left ventricular tissue revealed a predominant membrane-bound signal. Relative quantification of gene expression indicated that Kv4.2 and KChIP2 mRNA and protein are expressed at comparable ratios in porcine and rat left ventricular tissues, which displays a large I to. Collectively, these data demonstrate that the lack of a significant I to in the porcine left ventricle does not result from dysfunctional or insufficiently expressed Kv4.2 and KChIP2 sub-units.

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Acknowledgments

We are most grateful to R. Dussel and T. Kock for the technical assistance, and Priv. Doz. Dr. J. Zanzinger for the explantation of the porcine hearts. We gratefully acknowledge the donation of the Kv4.2 primary antibody by Prof. Dr. L.Y. Jan, and the donation of the pan-KChIP antibody by Prof. Dr. O. Pongs and Dr. D. Isbrandt. Supported by the Deutsche Forschungsgemeinschaft grants to H.E. and C.A.H (Graduiertenkolleg “Experimentelle Nieren- und Kreislaufforschung” and FOR 604).

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Authors and Affiliations

  1. Institut für Vegetative Physiologie und Pathophysiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany

    Jobst-Hendrik Schultz, Tilmann Volk, Peter Bassalaý & Heimo Ehmke

  2. Klinik für Innere Medizin II, Universitätsklinikum Heidelberg, INF 410, 69120, Heidelberg, Germany

    Jobst-Hendrik Schultz

  3. Institut für Zelluläre und Molekulare Physiologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Waldstraße 6, 91054, Erlangen, Germany

    Tilmann Volk

  4. Institut für Humangenetik, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany

    J. Christopher Hennings & Christian A. Hübner

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  1. Jobst-Hendrik Schultz
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  2. Tilmann Volk
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Correspondence to Heimo Ehmke.

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Schultz, JH., Volk, T., Bassalaý, P. et al. Molecular and functional characterization of Kv4.2 and KChIP2 expressed in the porcine left ventricle. Pflugers Arch - Eur J Physiol 454, 195–207 (2007). https://doi.org/10.1007/s00424-006-0203-1

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