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Hyperactivation of human sperm by 4-Aminopyridine: key role for mobilisation of stored Ca2+ in the sperm neck

Costello, Sarah Mary (2010)
Ph.D. thesis, University of Birmingham.

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Abstract

Within the female reproductive tract mammalian sperm gradually develop hyperactivated motility, triggered by increased flagellar Ca2+ resulting in deep flagellar bends. Two sources of Ca2+ may contribute to the regulation of hyperactivation. Ca2+ influx at the plasma membrane is crucial and the sperm specific CatSpers channels are of great importance. In addition, studies on sperm have provided strong evidence that Ca2+ stored in the region of the sperm neck contributes to regulation of flagellar activity. 4-aminopyridine caused robust and persistent hyperactivation of motility in human sperm. Ca2+ imaging showed that treatment with 4-aminopyridine induced a parallel elevation of [Ca2+]i, which initiated at the sperm neck/midpiece and was associated with asymmetric flagellar bending in this region. This report demonstrates that 4-aminopyridine induced hyperactivation in human sperm is not solely pH/CatSper channel dependent and that mobilisation of stored Ca2+, possibly causing activation of store-operated Ca2+ influx, is essential for hyperactivation in a population of human sperm. 4-aminopyridine induced IP3R and RyR store release in sacroplasmic reticulum and brain microsomal vesicles. Although the physiological factor(s) that activate hyperactivation in vivo remains elusive we can conclude that release of the neck/midpiece intracellular Ca2+ store was sufficient to initiate hyperactivation in a population of human sperm.

Type of Work:Ph.D. thesis.
School/Faculty:Colleges (2008 onwards) > College of Life & Environmental Sciences
Department:School of Biosciences
Subjects:QR Microbiology
Institution:University of Birmingham
ID Code:1320
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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