IMR Press / FBL / Volume 12 / Issue 4 / DOI: 10.2741/2158

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Article
Voltage-dependent calcium channels in mammalian spermatozoa revisited
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1 Fertility Research Laboratories, Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, New York, USA
2 Departments of Obstetrics and Gynecology, North Shore University Hospital, Manhasset, New York, USA
3 Departments of Obstetrics and Gynecology and Cell Biology, New York University School of Medicine, New York, New York, USA
4 Laboratory of Gene Activation, Center for Immunology and Inflammation, The Feinstein Institute for Medical Research, USA
5 Department of Medicine, North Shore University Hospital, Manhasset, New York, USA
6 Department of Medicine, New York University School of Medicine, New York, NY, USA
7 Department of Biological Sciences, Long Island University, Brookville, NY, USA
8 Division of Urology, Robert Wood Johnson School of Medicine, Camden, New Jersey, USA
9 Departments of Obstetrics and Gynecology and Medicine, University of Southern California, Los Angeles, California, USA
10 Core Research Facility, The Feinstein Institute for Medical Research, USA
11 350 Community Drive, Room 125, Manhasset, New York 11030, USA
Front. Biosci. (Landmark Ed) 2007, 12(4), 1420–1449; https://doi.org/10.2741/2158
Published: 1 January 2007
Abstract

The last few years have seen an explosion in the number of voltage-dependent ion channel sequences detected in sperm and testes. The complex structural paradigm of these channels is now known to include a pore-forming alpha1 subunit(s) whose electrophysiological properties are modulated by an intracellular beta subunit, a disulfide-linked complex of a membrane-spanning delta subunit with an extracellular alpha2 subunit, and a transmembrane gamma subunit. Many of these are alternatively spliced. Furthermore, the known number of genes coding each subtype has expanded significantly (10 alpha1, 4 beta, 4 alpha2delta, 8 gamma). Recently, the CatSper gene family has been characterized based on similarity to the voltage-dependent calcium channel alpha1 subunit. From among this multiplicity, a wide cross-section is active in sperm, including many splice variants. For example, expression of the various alpha1 subunits appears strictly localized in discrete domains of mature sperm, and seems to control distinct physiological roles such as cellular signaling pathways. These include alpha1 alternative splicing variants that are regulated by ions passed by channels in developing sperm. Various combinations of ion channel sequence variants have been studies in research models and in a variety of human diseases, including male infertility. For example, rats that are genetically resistant to testes damage by lead seem to respond to lead ions by increasing alpha1 alternative splicing. In contrast, in varicocele-associated male infertility, the outcome from surgical correction correlates with suppression of alpha1 alternative splicing, Ion channel blockers remain attractive model contraceptive drugs because of their ability to modulate cholesterol levels. However, the large number of sperm ion channel variants shared with other cell types make ion channels less attractive targets for male contraceptive development than a few years ago. In this review, the genetics, structure and function of voltage-dependent calcium channels and related CatSper molecules will be discussed, and several practical clinical applications associated with these channels will be reported.

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