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Calcium signalling in salivary gland physiology and dysfunction
Author(s) -
Ambudkar Indu S.
Publication year - 2015
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp271143
Subject(s) - orai1 , trpc , trpc3 , secretion , inositol trisphosphate receptor , salivary gland , microbiology and biotechnology , endocrinology , calcium signaling , medicine , calcium , transient receptor potential channel , inositol trisphosphate , inositol , chemistry , stim1 , signal transduction , receptor , biology
Studies over the past four decades have established that Ca 2+ is a critical factor in control of salivary gland function and have led to identification of the critical components of this process. The major ion transport mechanisms and ion channels that are involved in fluid secretion have also been established. The key event in activation of fluid secretion is an increase in [Ca 2+ ] i triggered by inositol 1,4,5‐trisphosphate (IP 3 )‐induced release of Ca 2+ from ER via the IP 3 receptor (IP 3 R). IP 3 Rs determine the site of initiation and the pattern of the [Ca 2+ ] i signal in the cell. However, Ca 2+ entry into the cell is required to sustain the elevation of [Ca 2+ ] i and fluid secretion and is mediated by the store‐operated Ca 2+ entry (SOCE) mechanism. Orai1, TRPC1, TRPC3 and STIM1 have been identified as critical components of SOCE in these cells. Cells finely tune the generation and amplification of [Ca 2+ ] i signals for regulation of cell function. An important emerging area is the concept that unregulated [Ca 2+ ] i signals in cells can directly cause cell damage, dysfunction and disease. Alternatively, aberrant [Ca 2+ ] i signals can also amplify and increase the rates of cell damage. Such defects in Ca 2+ signalling have been described in salivary glands in conjunction with radiation‐induced loss of salivary gland function as well as in the salivary defects associated with the autoimmune exocrinopathy Sjögren's syndrome. Such defects have been associated with altered function or expression of key Ca 2+ signalling components, such as STIM proteins and TRP channels. These studies offer new avenues for examining the mechanisms underlying the disease and development of novel clinical targets and therapeutic strategies.