Abstract
The calcium-sensing receptor (CaSR) is an extracellular Ca2+ sensor that plays a critical role in maintaining Ca2+ homeostasis in several organs, including the parathyroid gland and kidneys. In this study, through in situ hybridization, the expression of CaSR mRNA was found in the neuromasts of zebrafish larvae. Immunohistochemistry further demonstrated that the CaSR protein was present in neuromast hair cell stereocilia and basolateral membranes. Based on the expression and subcellular localization of the CaSR in hair cells, we hypothesized that the CaSR is expressed in zebrafish lateral-line hair cells to regulate mechanotransducer (MET)-channel-mediated Ca2+ entry. Using the scanning ion-selective electrode technique, MET-channel-mediated Ca2+ influx at the stereocilia of hair cells was measured in intact larvae. Ca2+ influx was suppressed after larvae were pretreated with a CaSR activator (R-568) or high-Ca2+ (HCa) medium. Gene knockdown by using morpholino oligonucleotides decreased CaSR expression in hair cells and eliminated the effects of R-568 and HCa on Ca2+ influx. In addition, we found that treatment with R-568 attenuated neomycin-induced hair cell death. This study is the first to demonstrate that the CaSR is involved in mechanotransduction in zebrafish hair cells.
Highlights
The calcium-sensing receptor (CaSR), a G-protein-coupled receptor, is activated by extracellular Ca2+ to regulate Ca2+ absorption and Ca2+ homeostasis in several organs, including the kidneys, intestines, bone, and parathyroid gland (Brown and MacLeod, 2001; Hofer and Brown, 2003; Smajilovic and Tfelt-Hansen, 2007)
Whole-mount In situ hybridization (ISH) was used to determine the localization of casr mRNA in 3-dpf zebrafish larvae
The selective electrode technique (SIET) was developed to enable the non-invasive measurement of ion flux in tissues or cells (Garber et al, 2005)
Summary
The calcium-sensing receptor (CaSR), a G-protein-coupled receptor, is activated by extracellular Ca2+ to regulate Ca2+ absorption and Ca2+ homeostasis in several organs, including the kidneys, intestines, bone, and parathyroid gland (Brown and MacLeod, 2001; Hofer and Brown, 2003; Smajilovic and Tfelt-Hansen, 2007). In the parathyroid gland, reduced plasma Ca2+ levels cause a CaSR-mediated increase in parathyroid hormone (PTH) secretion (Chattopadhyay and Brown, 2006). Loss-of-function mutations of the CaSR lead to decreased urinary Ca2+ excretion in humans and mice (Brown et al, 1998; Toka et al, 2012). These findings indicate that the CaSR plays a critical role in regulating Ca2+ homeostasis
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