Section: Science Life
New area of application for rapidly available cellular energy |
An incredible enzyme
The core of our sense of hearing is long thin cells that convert sound waves into electrical impulses. This conversion requires a very large amount of energy and the cells need to have special mechanisms to ensure continual replenishment of energy. Together with an international research team, ETH Zurich cell biologists have now shown that the enzyme creatine kinase plays a major role in the efficient supply of energy to these cells in the inner ear. Although the function of creatine kinase from the musculature has been known for a long time, it is now also being associated with hearing for the first time. Mice that lack this enzyme even lose part of their ability to hear.
Hearing is one of our most important senses. We need it not only to communicate but also to orientate ourselves in three dimensions. But how are we able to hear things anyway? One important requirement is sensory cells in the ears, which all other vertebrates also possess: the so-called mechanoreceptors. These cells – also called hair cells because of their shape in the ear – enable us to transform mechanical stimuli such as the movements of our eardrum into electrical impulses in our nerves.
This conversion of one kind of stimulus into a completely different type is costly for the cell and needs a very large amount of energy. To find out more about how the hair cells achieve this feat and which signal pathways are involved in the process, an international research team analysed all the active proteins in the hair cells of hens. This revealed that in addition to the usual structural proteins, for example actin, one enzyme above all is present in unusually large quantities: creatine kinase.
ETH Zurich Professor Theo Wallimann is a specialist in the creatine kinase area (1). He is a cell biologist who has worked with this unusual enzyme for thirty years, and together with German colleagues was even able to solve its crystal structure a few years ago. So it was no surprise when the American-Netherlands research team asked him to work with them to track down the function of creatine kinase in hearing. The results of this collaboration were published recently in an article in the scientific journal “Neuron” (2).
An enzyme for more energy
Creatine kinase is an enzyme whose function has long been known, mainly for muscle cells (3). Creatine kinase is responsible for phosphorylating creatine, i.e. it attaches a phosphate group to creatine, thus making it richer in energy. Because of its small size, the resulting phosphor-creatine can move freely in the cell and acts as a reserve store of energy to support ATP, the universal biological energy currency. This is why creatine kinase is found mainly in tissues that have a high and rapidly changing energy consumption.
Since not only the musculature but also the hearing consumes large amounts of energy, it is really not surprising that creatine kinase also plays an important role in the hair cells. However the concentration of this enzyme in the hair cells is even higher than in the musculature, which astonished the ETH Zurich researchers. As Wallimann explains “Why so much creatine kinase is used in the hair cells and whether this kinase is important to the sense of hearing, these were the questions that motivated us to this study.”
Hearing better thanks to creatine kinase
The most likely explanation for the presence of such large amounts of creatine kinase lies in the shape of the hair cells. Because these cells are so elongated, the energy must overcome very long distances from its production site – in the base of the cells – to the site of greatest consumption – at the tips of the processes. Crossing this long pathway efficiently is a big obstacle for ATP, because it interacts with every possible protein on the way and consequently the majority is used up prematurely.
The biologists have now shown that creatine kinase is directly involved in the transport of energy from the base to the tip of the hair cells and back again, thus supporting the energy flow. In contrast to ATP and its low-energy form ADP, phospho-creatine is metabolically inert and can cover the long distance without interruption. As a result the supply to the energy-greedy calcium pumps in the hair cell processes is always guaranteed. Wallimann explains that “This energy transport mechanism seems to be very successful, and is also used by other very long cells, for example nerves and spermatozoa.”
When the researchers specifically inhibited creatine kinase with a chemical, the flow of energy inside the hair cells was severely disturbed. Consequently the cells took longer to regenerate after a stimulus, causing deterioration in hearing performance. The research team also showed that mice completely lacking creatine kinase hear markedly worse than their peers. These animals also show disturbances of their sense of balance. Wallimann explains that “This is not very surprising either, since the balance organ also contains active hair cells that are stimulated depending on the movement of the body.”
As a food additive against hearing loss
Wallimann sees the treatment of hearing damage as one application of his research. The hair cells in the cochlea progressively die when exposed to prolonged loud noise stress such as frequent visits to discos. The ETH Zurich Professor now hopes that the destruction of the hair cells can be slowed by taking creatine as a food additive. Creatine has been permitted as a food supplement in Switzerland since 1995. It has been taken by athletes for a long time because of its beneficial effect in building muscle mass, primarily since it does not count as doping. The sprint and endurance properties of the muscles can be improved and their recovery time after hard training can be shortened by taking creatine.
The main reason that Wallimann expects creatine to influence hearing is that it has already been shown to have a protective effect on nerve cells. The researcher adds a cautionary note: “It is a purely preventive measure, however, since even creatine cannot revive cells once they have died.”
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