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Molecular Human Reproduction, Vol. 5, No. 4, 311-322, April 1999
© 1999 European Society of Human Reproduction and Embryology

Identification of structural elements of the testis-specific voltage dependent calcium channel that potentially regulate its biophysical properties

Leslie O. Goodwin1,4, Nina B. Leeds1, Dorothy Guzowski1, Ian R. Hurley2, Robert G. Pergolizzi1 and Susan Benoff2,3

1 Department of Research, North Shore University Hospital-New York University School of Medicine, Manhasset, New York, 2 Department of Obstetrics & Gynecology, North Shore University Hospital-New York University School of Medicine, 3 Departments of Obstetrics & Gynecology and Cell Biology, New York University School of Medicine

Calcium influx through voltage-dependent calcium channels regulates the physiological acrosome reaction of mammalian spermatozoa. Expression of the mRNA for these voltage-dependent calcium channels and its coordinated translation is initiated early in rat male germ line development and continues throughout spermatogenesis. Herein, we report the complete mRNA and deduced amino acid sequence of the {alpha}1C pore-forming subunit of the rat testis-specific L-type calcium channel. This subunit is transcribed from the {alpha}1C gene, which is also expressed in brain and cardiac muscle. The cardiac- and testis-specific isoforms of the {alpha}1C subunit are produced by alternate splicing of the same primary transcript. The testis-specific isoform differs from that of cardiac tissue at its amino terminus and in transmembrane segments IS6, IIIS2 and IVS3, which are also dihydropyridine binding sites. In somatic tissues, segments S2 and S3 regulate channel activation while the amino terminus and segment IS6 contribute to channel inactivation kinetics. The amino terminus and IS6 segment of the testis-specific {alpha}1C subunit are also expressed respectively, in the brain and in smooth muscle from lung where they alter the electrophysiological characteristics of the subunit to produce relatively slow inactivation kinetics. These findings provide a molecular explanation for the detection by others, by patch clamp analysis, of T-type calcium currents in immature spermatogenic cells and of atypical L-type calcium currents in mature spermatozoa.

acrosome reaction/alternative splicing/alternative promoters/calcium channel/calcium currents

4 To whom correspondence should be addressed


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