Bile acids induce Ca2+ signaling and membrane permeabilizations in vagal nodose ganglion neurons
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Bile acids induce Ca2+ signaling and membrane permeabilizations in vagal nodose ganglion neurons. / Mamedova, Esmira; Árting, Lív Bech; Rekling, Jens C.
In: Biochemistry and Biophysics Reports, Vol. 31, 101288, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Bile acids induce Ca2+ signaling and membrane permeabilizations in vagal nodose ganglion neurons
AU - Mamedova, Esmira
AU - Árting, Lív Bech
AU - Rekling, Jens C.
N1 - Publisher Copyright: © 2022 The Authors
PY - 2022
Y1 - 2022
N2 - Bile acids (BAs) play an important role in the digestion of dietary fats and act as signaling molecules. However, due to their solubilizing properties, high concentrations in the gut may negatively affect gut epithelium and possibly afferent fibers innervating the gastrointestinal tract (GI). To determine the effect of BAs on intracellular Ca2+ and membrane permeabilization we tested a range of concentrations of two BAs on vagal nodose ganglion (NG) neurons, Chinese Hamster Ovary (CHO), and PC12 cell lines. NG explants from mice were drop-transduced with the genetically encoded Ca2+ indicator AAV9-Syn-jGCaMP7s and used to measure Ca2+ changes upon application of deoxycholic acid (DCA) and taurocholic acid (TCA). We found that both BAs induced a Ca2+ increase in NG neurons in a dose-dependent manner. The DCA-induced Ca2+ increase was dependent on intracellular Ca2+ stores. NG explants, with an intact peripheral part of the vagus nerve, showed excitation of NG neurons in nerve field recordings upon exposure to DCA. The viability of NG neurons at different BA concentrations was determined, and compared to CHO and PC12 cells lines using propidium iodide labeling, showing threshold concentrations of BA-induced cell death at 400–500 μM. These observations suggest that BAs act as Ca2+-inducing signaling molecules in vagal sensory neurons at low concentrations, but induce cell death at higher concentrations, which may occur during inflammatory bowel diseases.
AB - Bile acids (BAs) play an important role in the digestion of dietary fats and act as signaling molecules. However, due to their solubilizing properties, high concentrations in the gut may negatively affect gut epithelium and possibly afferent fibers innervating the gastrointestinal tract (GI). To determine the effect of BAs on intracellular Ca2+ and membrane permeabilization we tested a range of concentrations of two BAs on vagal nodose ganglion (NG) neurons, Chinese Hamster Ovary (CHO), and PC12 cell lines. NG explants from mice were drop-transduced with the genetically encoded Ca2+ indicator AAV9-Syn-jGCaMP7s and used to measure Ca2+ changes upon application of deoxycholic acid (DCA) and taurocholic acid (TCA). We found that both BAs induced a Ca2+ increase in NG neurons in a dose-dependent manner. The DCA-induced Ca2+ increase was dependent on intracellular Ca2+ stores. NG explants, with an intact peripheral part of the vagus nerve, showed excitation of NG neurons in nerve field recordings upon exposure to DCA. The viability of NG neurons at different BA concentrations was determined, and compared to CHO and PC12 cells lines using propidium iodide labeling, showing threshold concentrations of BA-induced cell death at 400–500 μM. These observations suggest that BAs act as Ca2+-inducing signaling molecules in vagal sensory neurons at low concentrations, but induce cell death at higher concentrations, which may occur during inflammatory bowel diseases.
KW - Bile acids
KW - Ca signaling
KW - Pathology
KW - Vagal afferents
U2 - 10.1016/j.bbrep.2022.101288
DO - 10.1016/j.bbrep.2022.101288
M3 - Journal article
C2 - 35669985
AN - SCOPUS:85131128966
VL - 31
JO - Biochemistry and Biophysics Reports
JF - Biochemistry and Biophysics Reports
SN - 2405-5808
M1 - 101288
ER -
ID: 314450007