Temperature sensitivity of connexin 26
23 April 2019 (online)
Rapid opening and closing of the connexons (connexin hemi channels) allows the transport of small molecules between adjacent cells. In the inner ear, this leads to the formation and preservation of the endocochlear potential and thus to the physical basis of hearing. Disorders of homeostasis lead to hearing loss. In preliminary studies, we were able to show that patients with heterozygous connexin mutations despite initial perfect inner ear function lose their hearing of time. Pathologies associated with changes in the physical environment such as coclear inflammation, which is associated with a change in temperature, could be responsible for this. However, there is no screening procedure to evaluate the patient-specific risk potential.
The activity of the connexin 26 hemichannels was measured as function of temperature. This was done using a liposome vesicle flux assay directly on the protein in vitro. Xenopus-oocytes injected with human variants of connexin 26 were used as a reference system.
The temperature-dependent opening of the connexin hemichannels could be demonstrated directly at the protein and was verified with the established frog oocyte model.
Summary: The present results could provide the basis for the development of a valid microarray for a patient-specific screening, with which the sensitivity of temperature changes of hemichannels can be determined.