Regulation of Cellular Calcium in Vestibular Supporting Cells by Otopetrin 1
Year: 2010
Type: article
Abstract: Otopetrin 1 (OTOP1) is a multitransmembrane domain protein, which is essential for mineralization of otoconia, the calcium carbonate biominerals required for vestibular function, and the normal sensation of gravity. The mechanism driving mineralization of otoconia is poorly understood, but it has been proposed that supporting cells and a mechanism to maintain high concentrations of calcium are critical. Using Otop1 knockout mice and a utricular epithelial organ culture system, we show that OTOP1 is expressed at the apex of supporting cells and functions to increase cytosolic calcium in response to purinergic agonists, such as adenosine 5'-triphosphate (ATP). This is achieved by blocking mobilization of calcium from intracellular stores in an extracellular calcium-dependent manner and by mediating influx of extracellular calcium. These data support a model in which OTOP1 acts as a sensor of the extracellular calcium concentration near supporting cells and responds to ATP in the endolymph to increase intracellular calcium levels during otoconia mineralization.
Source: Journal of Neurophysiology
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Awards: Research Core Center for Auditory and Vestibular Studies, Washington University Center for Translational Neuroscience, G3647780438, G4549778172, OTOCONIA DEVELOPMENT AND MAINTENANCE, G5973595807, BIOLOGICAL FUNCTION OF THE OTOPERTRIN GENE FAMILY, OLIGODENDROCYTE DEATH IN CEREBRAL ISCHEMIA, Cell-Cell Interaction and Hypoxic Brain Injury, G822165535, Cancer Center Support Grant, Host-environment interactions in the pathophysiology of digestive disease
OpenAlex ID: W2100984050