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Researchers identify molecule that senses osmotic pressure in vertebrates

Hughes Medical Institute. Heller is now an assistant professor at Harvard Medical School. Liedtke discovered VR-OAC while looking in a region of the brain called the hypothalamus for genes operative in the regulation of body temperature. The hypothalamus monitors and regulates a score of vital parameters in the body, including osmotic pressure, energy balance and temperature. Of those, systemic osmotic pressure is the most aggressively defended setpoint value in vertebrate animals including humans. An increase in osmotic pressure leads to the sense of thirst and drinking behavior, and osmoreceptors in the hypothalamus send signals to nerve cells that manufacture antidiuretic hormone (ADH), the primary regulator of body water.

Liedtke found VR-OAC expressed in neurons in brain structures called the circumventricular organs. Most of the brain is protected by the blood-brain barrier, a gateway that allows only certain substances to pass into the brain. The circumventricular organs are located inside the brain, but outside the blood-brain barrier. Circumventricular organs are recognized as important sites for communication of the central nervous system with the remainder of the organism through the blood/serum.

Liedtke collaborated with Heller and colleagues in the Laboratory of Sensory Neuroscience who had cloned VR-OAC from a chicken inner ear gene library. Liedtke thought that VR-OAC could be an ion channel that responds to osmotic pressure. They showed that VR-OAC was also present in hair cells of the inner ear, which Hudspeth's lab has studied and functionally characterized. These cells are the principal mechanotransductory cells essential for the perception of sound and the sensing of acceleration in the inner ear's sense of equilibrium. VR-OAC may be key in helping to regulate the salt and water household of these cells.

"As an alternative model and a more general concept, VR-OAC could be part of sensory cells' mechanosensitive molecular apparat
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Contact: Joseph Bonner
bonnerj@mail.rockefeller.edu
212-327-7900
Rockefeller University
25-Oct-2000


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