Costello, Sarah Mary (2010). Hyperactivation of human sperm by 4-Aminopyridine: key role for mobilisation of stored Ca2+ in the sperm neck. University of Birmingham. Ph.D.
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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: | Thesis (Doctorates > Ph.D.) |
|---|---|
| Award Type: | Doctorates > Ph.D. |
| Licence: | |
| College/Faculty: | Colleges (2008 onwards) > College of Life & Environmental Sciences |
| School or Department: | School of Biosciences |
| Funders: | None/not applicable |
| Subjects: | Q Science > QR Microbiology |
| URI: | http://etheses.bham.ac.uk/id/eprint/1320 |
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