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However, said Clapham, the constant wriggling of spermatozoa, as well as the way their tough membranes stretch tightly stretched over underlying structures, made the cells incompatible with this research technique.

"Back in 2001, we made more than a thousand attempts to patch clamp sperm without success," said Clapham. "We had been quite frustrated by it. However, Yuriy finally discovered a way to patch clamp the cells, which was central to the success reported in this paper." Basically, Kirichok found that he could patch clamp the pipette into a microscopic "cytoplasmic droplet" that is present in sperm before ejaculation, but is usually lost in mature sperm.

Patch clamp studies on spermatozoa with remnant cytoplasmic droplets revealed that CatSper1 was a major component of the calcium ion channel responsible for alkaline-activated hyperactivation and male fertility.

According to Clapham, the finding represents the beginning of an important new research pathway. "It's like opening an chamber in an ancient pyramid, because no one had ever seen inside sperm cells to measure all the currents that control their activity," he said. "We are already measuring many of these currents and beginning to answer questions about what they are and what they do."

Further studies, said Clapham, will aim at exploring the many controlling currents inside sperm and also tracing how calcium triggers hyperactivation once it enters the cell. Such studies will enable exploration of sperm machinery from tail to head ?analyzing processes ranging from tail motility to the mechanism by which the sperm head delivers its genetic payload to the egg, he said.

Such research could yield insight into some male infertility, said Clapham. Still-unidentified mutations in any of the four CatSper proteins ?all of which are invol
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Source:Howard Hughes Medical Institute