Few biological images have worked their way into the popular imagination more successfully than the sperm cell. You needn't have ever opened a science textbook to recognize that formidable little swimmer propelled by a tadpole-like tail.

But until recently, imagination (as opposed to genuine knowledge) was all scientists could bring to bear on the understanding of spermatozoa, because the intimate details of their lives were hidden within “ion channels”—networks of pore-forming proteins that help regulate the cells' electrochemical activity. While standard laboratory techniques used to eavesdrop on ion-channel functioning have worked fine for most other types of cells, sperm cells proved resistant—until a research team led by HHMI investigator David E. Clapham, a neurobiologist at Harvard Medical School, found a way around the problem.

In 2001, Clapham discovered a particular ion channel, which he named CatSper1, unique to the sperm's tail. This channel appeared to be necessary for the sperm to enter into “hyperactivation,” the process that enables it to penetrate the egg.

Young, immature sperm cells tend to swim in an orderly, highly symmetrical pattern. But as they travel farther into the vaginal canal and enter the alkaline environment housing the egg, their pattern changes. As hyperactivation begins, the sperm's swimming pattern becomes less symmetrical. The tail assumes a whip-like motion, enabling it to strike the egg's surface with greater force. When Clapham “knocked out”—that is, inactivated—the gene for CatSper1 in mouse sperm cells, 100 percent of the mice became infertile.

Normally, when researchers want a closer look at an ion channel of interest, they use a technique called patch-clamp recording. In this routine procedure, an electrode provides a window through the membrane into the cell's machinations. In addition, researchers can introduce various chemicals and substrates through the probe to manipulate and study the cell's properties.

Illustration: Jeffrey Decoster

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