05 February 2010

Proton-driven spermatozoa

By assessing the electric current passing through the sperm membrane, researchers at the University of California at San Francisco (pay attention to their surnames - whether to rejoice at this, or vice versa) identified a membrane channel that releases a stream of protons from the sperm, which triggers its movement up the fallopian tube towards the egg. The results obtained by the authors are published in the journal Cell on February 5 in the article Polina V. Lishko, Inna L. Botchkina, Andriy Fedorenko, Yuriy Kirichok "Acid Extrusion from Human Spermatozoa Is Mediated by Flagellar Voltage-Gated Proton Channel".

Spermatozoa resting inside the seminal glands are motionless. However, after ejaculation, when sperm enters the vagina, the pH level inside the spermatozoa increases (i.e. shifts to the alkaline side), which triggers their movement towards the fallopian tubes. After the first jerk, they get stuck for a while in the sticky folds of the mucous membrane covering the fallopian tube and rest until a new, unencrypted mechanism to date again increases their intracellular pH level and initiates their final race on the way to the egg. This sequence of events has been known to scientists for decades, but many aspects of the mechanisms that trigger it still remain a mystery.

Inside the resting spermatozoa contains a huge number of protons. At the moment of activation, the protein – proton channel Hv1 identified by the authors forms a pore in the sperm membrane through which the cell literally throws out a stream of protons, which sets it in motion. (In the picture, the Hv1 protein is colored green, the blue spots are sperm nuclei, the red ones are mitochondria.)

The authors identified the Hv1 proton channel using a technique developed by Kirichok in 2006, which for the first time allowed the method of local potential fixation (or "patch-clamp", from the English patch-clamp) to be applied to human spermatozoa. To implement this method, tiny glass electrodes are attached to the sperm cells to measure the flow of ions crossing the cell membrane. This gave the authors the opportunity to observe protons actively released by the cell through proton channels in real time.

For several decades, researchers have unsuccessfully attempted to conduct a similar experiment. The method of local potential fixation is widely used to study various types of cells, but so far no one has been able to apply it to human spermatozoa, which are much smaller than mice.

Researchers are not yet aware of the mechanisms that open the Hv1 channel. One possible explanation is that a change in the external pH level when a sperm enters the vagina can initiate the movement of ions from the cell through the membrane channel. According to another hypothesis, the activity of proton channels is blocked by zinc ions contained in spermatozoa, which are easily absorbed by the mucous membrane of the vagina and fallopian tubes. It is possible that the period of sperm dormancy in the fallopian tubes continues until a sufficient amount of zinc ions leaves the cell, which is the signal for the final race.

The Hv1 channel also opens in the presence of endocannabinoid compounds, normally present in both the male and female reproductive tract. Marijuana smokers may have problems with conception due to tetrahydrocannabinol contained in the "weed", which excessively activates proton channels, which can lead to premature sperm death.

The authors believe that their finding opens up new prospects in the development of both contraceptives and drugs for the treatment of male infertility. Kirichok also adds that the release of protons from spermatozoa is triggered by the physiology of the female body, therefore, if in the future specialists manage to create contraceptives based on Hv1 channel blockers, they will be intended primarily for women, although it is theoretically possible to create "unisex" options.

However, experts note that Hv1 channels are found in many cells of the body, especially in cells of the immune system, which will significantly complicate the development of such drugs.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of The Scientist: Sperm motility secrets revealed.

05.02.2010

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