Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Molecular identification of a hyperpolarization-activated channel in sea urchin sperm

Nature volume 393, pages 583–587 (1998)Cite this article

Abstract

Sea urchin eggs attract sperm through chemotactic peptides, which evoke complex changes in membrane voltage and in the concentrations of cyclic AMP, cyclic GMP and Ca2+ ions (see ref. 1 for a review). The intracellular signalling pathways and their cellular targets are largely unknown. We have now cloned, from sea urchin testis, the complementary DNA encoding a channel polypeptide, SPIH. Functional expression of SPIH gives rise to weakly K+-selective hyperpolarization-activated channels, whose activity is enhanced by the direct action of cAMP. Thus, SPIH is under the dual control of voltage and cAMP. The SPIH channel, which is confined to the sperm flagellum, may be involved in the control of flagellar beating. SPIH currents exhibit all the hallmarks of hyperpolarization-activated currents (Ih)2,3, which participate in the rhythmic firing of central neurons, control pacemaking in the heart, and curtail saturation by bright light in retinal photoreceptors2,3. Because of their sequence4 and functional properties, Ih channels form a class of their own within thesuperfamily of voltage-gated and cyclic-nucleotide-gated channels.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The SPIH channel belongs to the superfamily of voltage- and cyclic-nucleotide-gated channels.
Figure 2: Site of expression of the SPIH channel in S. purpuratus.
Figure 3: The SPIH channel opens by hyperpolarization.
Figure 4: Modulation of the SPIH channel by cAMP.
Figure 5: Pharmacological characterization of the SPIH channel.

Similar content being viewed by others

References

  1. Ward, C. R. & Kopf, G. S. Molecular events mediating sperm activation. Dev. Biol. 158, 9–34 (1993).

    Article  CAS  Google Scholar 

  2. DiFrancesco, D. Pacemaker mechanisms in cardiac tissue. Annu. Rev. Physiol. 55, 455–472 (1993).

    Article  CAS  Google Scholar 

  3. Pape, H.-C. Queer current and pacemaker: the hyperpolarization-activated cation current in neurons. Annu. Rev. Physiol. 58, 299–327 (1996).

    Article  CAS  Google Scholar 

  4. Santoro, B., Grant, S. G. N., Bartsch, D. & Kandel, E. R. Interactive cloning with the SH3 domain of N-src identifies a new brain specific ion channel protein, with homology to Eag and cyclic nucleotide-gated channels. Proc. Natl Acad. Sci. USA 94, 14815–14820 (1997).

    Article  ADS  CAS  Google Scholar 

  5. Heginbotham, L., Abramson, T. & MacKinnon, R. Afunctional connection between the pores of distantly related ion channels as revealed by mutant K+ channels. Science 258, 1152–1155 (1992).

    Article  ADS  CAS  Google Scholar 

  6. Heginbotham, L., Lu, Z., Abramson, T. & MacKinnon, R. Mutations in the K+ channel signature sequence. Biophys. J. 66, 1061–1067 (1994).

    Article  CAS  Google Scholar 

  7. Finn, J. T., Grunwald, M. E. & Yau, K.-W. Cyclic nucleotide-gated ion channels: an extended family with diverse functions. Annu. Rev. Physiol. 58, 395–426.

  8. DiFrancesco, D. Characterization of the pace-maker current kinetics in calf Purkinje fibres. J. Physiol. 348, 341–367 (1984).

    Article  CAS  Google Scholar 

  9. Hagen, V.et al. Caged compounds of hydrolysis-resistant analogues of cAMP and cGMP: synthesis and application to cyclic nucleotide-gated channels. Biochemistry 35, 7762–7771 (1996).

    Article  CAS  Google Scholar 

  10. DiFrancesco, D. & Mangoni, M. Modulation of single hyperpolarization-activated channels (If) by cAMP in the rabbit sino-atrial node. J. Physiol. 474, 473–482 (1994).

    Article  CAS  Google Scholar 

  11. Beavo, J. A. Cyclic nucelotide phosphodiesterases: functional implications of multiple isoforms. Physiol. Rev. 75, 725–748 (1995).

    Article  CAS  Google Scholar 

  12. Wollmuth, L. P. & Hille, B. Ionic selectivity of Ihchannels of rod photoreceptors in tiger salamanders. J.Gen. Physiol. 100, 749–765 (1992).

    Article  CAS  Google Scholar 

  13. DiFrancesco, D. & Tortora, P. Direct activation of cardiac pacemaker channels by intracellular cyclic AMP. Nature 351, 145–147 (1991).

    Article  ADS  CAS  Google Scholar 

  14. Trudeau, M. C., Warmke, J. W., Ganetzky, B. & Robertson, G. A. HERG, a human inward rectifier in the voltage-gated potassium channel family. Science 269, 92–95 (1995).

    Article  ADS  CAS  Google Scholar 

  15. Smith, P. L., Baukrowitz, T. & Yellen, G. The inward rectification mechanism of the HERG cardiac potassium channel. Nature 379, 833–836 (1996).

    Article  ADS  CAS  Google Scholar 

  16. Labarca, P.et al. AcAMP regulated K+-selective channel from the sea urchin sperm plasma membrane. Dev. Biol. 174, 271–280 (1996).

    Article  CAS  Google Scholar 

  17. Babcock, D. F., Bosma, M. M., Battaglia, D. E. & Darszon, A. Early persistent activation of sperm K+ channels by the egg peptide speract. Proc. Natl Acad. Sci. USA 86, 6001–6005 (1992).

    Article  ADS  Google Scholar 

  18. Hansbrough, J. R. & Garbers, D. L. Speract — purification and characterization of a peptide associated with eggs that activates spermatozoa. J. Biol. Chem. 256, 1447–1452 (1981).

    CAS  PubMed  Google Scholar 

  19. Darszon, A., Labarca, P., Beltrán, C., García-Soto, J. & Liévano, A. Sea urchin sperm: an ion channel reconstitution study case. Methods: a Companion Methods Enzymol. 6, 37–50 (1994).

    Article  CAS  Google Scholar 

  20. Bönigk, W.et al. Rod and cone photoreceptor cells express distinct genes for cGMP-gated channels. Neuron 10, 865–877 (1993).

    Article  Google Scholar 

  21. Baumann, A., Frings, S., Godde, M., Seifert, R. & Kaupp, U. B. Primary structure and functional expresion of a Drosophila cyclic nucleotide-gated channel present in eyes and antennae. EMBO J. 13, 5040–5050 (1994).

    Article  CAS  Google Scholar 

  22. Pongs, O.et al. Shaker encodes a family of putative potassium channel proteins in the nervous system of Drosophila. EMBO J. 7, 1087–1096 (1988).

    Article  CAS  Google Scholar 

  23. Warmke, J., Drysdale, R. & Ganetzky, B. Adistinct potassium channel polypeptide encoded by the Drosophila eag locus. Science 252, 1560–1562 (1991).

    Article  ADS  CAS  Google Scholar 

  24. Warmke, J. W. & Ganetzky, B. Afamily of potassium channel genes related to eag in Drosophila and mammals. Proc. Natl Acad. Sci. USA 91, 3438–3442 (1994).

    Article  ADS  CAS  Google Scholar 

  25. Anderson, J. A., Huprikar, S. S., Kochian, L. V., Lucas, W. J. & Gaber, R. F. Functional expression of a probable Arabidopsis thaliana potassium channel in Saccharomyces cerevisiae. Proc. Natl Acad. Sci. USA 89, 3736–3740 (1992).

    Article  ADS  CAS  Google Scholar 

  26. Kaupp, U. B.et al. Primary structure and functional expression from complementary DNA of the rod photoreceptor cyclic GMP-gated channel. Nature 342, 762–766 (1989).

    Article  ADS  CAS  Google Scholar 

  27. Ludwig, J., Margalit, T., Eismann, E., Lancet, D. & Kaupp, U. B. Primary structure of cAMP-gated channel from bovine olfactory epithelium. FEBS Lett. 270, 24–29 (1990).

    Article  CAS  Google Scholar 

  28. Titani, K.et al. Amino acid sequence of the regulatory subunit of bovine type I adenosine cyclic 3′,5′-phosphate dependent protein kinase. Biochemistry 23, 4193–4199 (1984).

    Article  CAS  Google Scholar 

  29. Takio, K.et al. Guanosine cyclic 3′,5′-phosphate dependent protein kinase, a chimeric protein homologous with two separate protein families. Biochemistry 23, 4207–4218 (1984).

    Article  CAS  Google Scholar 

  30. Aiba, H., Fujimoto, S. & Ozaki, N. Molecular cloning and nucleotide sequencing of the gene for E. coli cAMP receptor protein. Nucleic Acids Res. 10, 1345–1361 (1982).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank H. Breer for providing a cDNA clone that encodes a Heliothes SPIH homologue; J. E. Brown, E. Eismann, and I. Weyand for careful reading of the manuscript; A. Eckert for preparing the manuscript; and H. Schauf for the illustrations. R.G. was the recipient of a stipend from the Boehringer Ingelheim Fonds.

Author information

Author notes

  1. Renate Gauss and Reinhard Seifert: These authors contributed equally to this work.

Authors and Affiliations

  1. Institut für Biologische Informationsverarbeitung, Forschungszentrum Jülich, Jülich, D-52425, Germany

    U. Benjamin Kaupp

Authors
  1. Renate Gauss
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Reinhard Seifert
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. U. Benjamin Kaupp
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to U. Benjamin Kaupp.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gauss, R., Seifert, R. & Kaupp, U. Molecular identification of a hyperpolarization-activated channel in sea urchin sperm. Nature 393, 583–587 (1998). https://doi.org/10.1038/31248

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/31248

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing