Saliva is essential to eating and swallowing food, but what causes the salivary gland to secrete it? Researchers at the University of Rochester Medical Center have analyzed the interplay between a protein called the IP3 receptor and calcium in saliva’s production, which could lead to improved treatments for Sjögren’s syndrome and other diseases.
Calcium is present in all of our cells. As its levels increase, “gates” or “channels” required for the production and secretion of saliva and other bodily fluids open up. If calcium levels don’t increase, these gates won’t open, leading to dry mouth and difficulties in chewing, swallowing, and speaking. Opening these channels, then, would be key to treatment.
The IP3 receptor is necessary in increasing calcium and generating channels in many, if not all, cells. But one channel is created from 4 identical units in the receptor, and, until now, it was not known how many of the individual units had to be engaged for the channel to work.
Using advanced molecular engineering and gene editing techniques, the researchers discovered that all 4 parts must be activated for calcium to increase in a cell and start processes like fluid secretion without exception.
The calcium channel, then, only opens under strict conditions that result in secretions, avoiding harmful events that would occur if the channel could open more easily. For example, too much calcium can lead to processes that kill cells.
“The results have broad implications not only for how calcium is controlled in cells, but also for understanding various human secretory disorders that range from dry mouth to pancreatitis,” said Robert T. Dirksen, PhD, the Lewis Pratt Ross professor and chair of the department of pharmacology and physiology at the University of Rochester School of Medicine and Dentistry.
“Our hope is that better knowledge of the mechanisms that control the flow of calcium in and out of cells will advance research on new treatments for many diseases, including Sjögren’s,” said David I. Yule, PhD, also a professor with the department of pharmacology and physiology as well as the Center for Oral Biology and the department of medicine, gastroenterology/hepatology.
The study, “Defining the Stoichiometry of Inositol 1,4,5-triphosphate Binding Required to Initiate Ca2+ Release,” was funded by the National Institute of Dental and Craniofacial Health and published by Science Signaling.
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