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

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.

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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.

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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.

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Correspondence to U. Benjamin Kaupp.

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