The ability to measure sperm currents has also enabled the researchers to pin down the role of a protein called CatSper that is vital for male fertility -- establishing CatSper as a target for developing a male contraceptive.
CatSper, discovered in 2001 in the Children's Hospital Boston lab of David Clapham, MD, PhD, is found only in the tails of mature sperm. Mice that lacked CatSper were completely infertile: their sperm were poor swimmers and couldn't penetrate the protective barriers around the egg. But no one was sure what role CatSper played or how it worked.
By directly measuring electrical activity, the new experiments, conducted by Yuriy Kirichok, PhD and Betsy Navarro, PhD, were able to show that CatSper is a key channel by which calcium ions enter the sperm's tail. The calcium influx, measurable as an electrical current, "hyperactivates" the tail's motor proteins, giving the sperm the burst of swimming power needed to reach the egg. The current was detectable in sperm from normal mice, but not in sperm from mice that lacked CatSper.
"Now, people can directly test modulators of CatSper," Navarro says. "If they find something that blocks the current, it could be used as a male contraceptive. Before, people didn't know what the exact target was, and didn't have a system to test drugs."
Hydra Biosciences (Cambridge, Mass.), a biotech company co-founded by Clapham, is pursuing a drug that would block CatSper. The challenge will be to develop a drug that blocks only CatSper and not other calcium channels, which occur throughout the body.
Electrical activity has long been known to be importan
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Contact: Bess Andrews
elizabeth.andrews@childrens.harvard.edu
617-355-6420
Children's Hospital Boston
8-Feb-2006