Sperm’s pore propulsion

Researchers identify proton channel that helps regulate frantic dash

Fancy goggles, a swimming cap or the latest high-tech suit won’t help human sperm power through their race to fertilize an egg. Instead, the tiny cells rely on a proton-shedding pore to speed toward their target, a study in the Feb. 5 Cell finds.

SWIMMING SECRET Sperm swim with the help of a proton channel recently identified by scientists. The proton channel Hv1 (shown here in green) is abundant on the tails, or flagella, of human sperm. DNA (blue) and power-producing mitochondria (red) are also shown. Yuriy Kirichok

The study also reports that a compound similar to the active ingredient in marijuana might interfere with this channel, offering a molecular link between habitual marijuana use and male infertility. Finding other compounds that open or close the channel may offer new ways to control reproduction, the authors say.

Researchers knew that powerful sperm swimming depends on protons leaving the sperm cell, thereby lowering its acidity. The concentration of protons inside a sperm is roughly 1,000 times higher than outside, says a coauthor of the new study, Yuriy Kirichok, a biophysicist at the University of California, San Francisco. As protons flood out of the cell like air let out of a balloon, a host of changes kick the sperm’s swimming into high gear. But just how the protons escaped was a mystery.

“This is an important paper because it reveals how human spermatozoa lower intracellular acidity,” comments David Clapham, a Howard Hughes Medical Institute investigator at Harvard Medical School in Boston.

Kirichok and his colleagues used a technique called patch clamping to examine the electrical properties of mature human sperm. Grabbing the sperm cells with a tiny glass pipette, the researchers used an electrode to record proton movement across the cell membranes. The electrical properties of the sperm were very similar to those of certain immune cells that are known to discharge protons through a channel called Hv1.

Next, to verify that Hv1 was the correct channel in sperm, Kirichok and colleagues used green fluorescent antibodies that specifically stain that channel. The tails, or flagella, of the human sperm cells glowed green, indicating that the channel was abundant there, the team found.

The researchers also looked for substances that changed Hv1’s behavior. A compound called anandamide, which is similar to the active ingredient in marijuana, opened the channel. “It’s been known for quite some time that marijuana reduces fertility, but nobody knows why this happens,” Kirichok says. “We for the first time show the presence of a molecule on sperm that can be directly activated by anandamide.” He speculates that habitual marijuana use may activate sperm cells — via Hv1 — prematurely, leaving them burned out and unable to swim when it counts.

Finding this proton channel required for swimming could lead to new insights on the details of human sperm activity — specifically how molecular signals control sperm behavior during fertilization, comments Dejian Ren of the University of Pennsylvania in Philadelphia. What’s more, identifying compounds that can tweak sperm swimming by opening or closing Hv1’s proton pore may ultimately give scientists new ways to control fertility, the study’s authors note.

Laura Sanders is the neuroscience writer. She holds a Ph.D. in molecular biology from the University of Southern California.

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