Slo1 is the principal potassium channel of human spermatozoa

Abstract

Mammalian spermatozoa gain competence to fertilize an oocyte as they travel through the female reproductive tract. This process is accompanied by an elevation of sperm intracellular calcium and a membrane hyperpolarization. The latter is evoked by K ⁺ efflux; however, the molecular identity of the potassium channel of human spermatozoa (hKSper) is unknown. Here, we characterize hKSper, reporting that it is regulated by intracellular calcium but is insensitive to intracellular alkalinization. We also show that human KSper is inhibited by charybdotoxin, iberiotoxin, and paxilline, while mouse KSper is insensitive to these compounds. Such unique properties suggest that the Slo1 ion channel is the molecular determinant for hKSper. We show that Slo1 is localized to the sperm flagellum and is inhibited by progesterone. Inhibition of hKSper by progesterone may depolarize the spermatozoon to open the calcium channel CatSper, thus raising [Ca ²⁺] to produce hyperactivation and allowing sperm to fertilize an oocyte.

DOI: http://dx.doi.org/10.7554/eLife.01009.001

eLife digest

The sperm cells that are released into the female reproductive tract when a mammal ejaculates, are not capable of fertilizing an egg right away, so they must go through a process called maturation. The early stages of this process involve interactions with the seminal fluid that increase the motility of the sperm cells, and the latter stages involve interactions with the walls of the reproductive tract and vaginal secretions to ensure that the sperm cells move toward the egg. Many of these interactions involve positive ions entering and leaving the sperm cells via ion channels.

The properties of the ion channels that allow protons and calcium ions to move into and out of human sperm cells are well understood, but little is known about the channels that control the movement of the potassium (K) ions. At first it was assumed that the molecular structure of these channels was similar to that of the Slo3 potassium channel in mouse sperm, but crucial differences between human and mouse sperm cells have been reported in recent years.

Now Mannowetz et al. have shown that the potassium channel in human sperm is opened by increased levels of calcium ions inside the sperm cells. Moreover, the pH inside the sperm cells had no influence on this process. Furthermore, the channel was blocked by three toxins that have no effect on the Slo3 potassium channels in mice, but are known to block a type of potassium channel known as Slo1. Mannowetz et al. then used a technique called Western blotting to confirm the presence of Slo1 potassium channels in the tails of human sperm cells.

Mannowetz et al. also showed that the Slo1 potassium channel can be blocked by the female hormone progesterone. This is important because blocking the potassium channels causes the calcium ion channels in the cells to open fully, and the resulting influx of calcium ions triggers a process called sperm hyperactivation that makes it possible for the sperm cell to fertilize the egg. By clearly showing the fundamental differences between human sperm cells and mouse sperm cells, this work stresses the need to exercise caution in using mice as a model of male fertility in humans.

DOI: http://dx.doi.org/10.7554/eLife.01009.002