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Enteric Glial Cells Acutely Regulate Secretomotor Function in The Mouse Colon
Author(s) -
Grubisic Vladimir,
Gulbransen Brian D.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1010.6
Subject(s) - veratridine , neuroglia , tetrodotoxin , glial fibrillary acidic protein , ion channel , ion transporter , microbiology and biotechnology , chemistry , biology , biophysics , endocrinology , biochemistry , sodium channel , sodium , central nervous system , receptor , immunology , immunohistochemistry , organic chemistry , membrane
Enteric glial cells are implicated in the regulation of epithelial barrier and secretomotor functions of the intestines. But whether glial cell activity regulates these functions acutely under physiological conditions is not clear. We addressed this issue by using transgenic animal models to modify the activity of enteric glia, either reducing glial expression of connexin 43 in Sox10:: CreER T2+/− /Cx43 f/f mice or activating glial calcium responses in GFAP ::hM3Dq mice, and tested the effects on colonic barrier function and electrogenic ion transport in Ussing chambers. We assess neuronal dependent and independent contributions by activating or inhibiting neurogenic activity with veratridine and tetrodotoxin, respectively. Our results show that the reduction of glial Cx43 expression in Sox10:: CreER T2+/− /Cx43 f/f mice significantly reduced neurogenic ion transport to 75 ± 5 % (mean ± SEM) of the paired littermate controls ( P = 0.004, One sample t ‐test, n = 6 animals per group). The selective glial activation in tissues from GFAP ::hM3Dq mice evoked electrogenic ion transport to an equal extent as the direct activation of neurogenic ion transport with veratridine (74 ± 9 vs. 75 ± 2 % of the responses to secretagogue forskolin) and glial driven responses consisted of both tetrodotoxin sensitive and insensitive components. The selective glial stimulation did not affect transmural ion conductance or cell‐impermeant dye flux but the baseline ion conductance was more variable in Sox10:: CreER T2+/− /Cx43 f/f tissues. Together, our findings show that glial activity contributes to the regulation of electrogenic ion transport in the intestine through effects on neurons and possibly direct effects on epithelial cells. However, the influence of glia on gut barrier function seems to involve tonic, rather than acute, mechanisms. These findings provide novel insight into the cellular mechanisms that control fluid transport homeostasis in the intestine ( Figure). In addition, these observations raise the possibility that enteric glial activation plays a role in functional diarrheal diseases and that the selective manipulation of glia could be beneficial to improve treatment and patient quality of life. Support or Funding Information Dr. Gulbransen's research is currently supported by grants from the Crohn's and Colitis Foundation of America (CCFA; Senior Research Award) and the National Institutes of Health (NIH; RO1DK103723).Enteric glial activity regulates intestinal ion transport. Selective glial stimulation has an equal effect as direct activation of neurogenic ion transport. Neuron depolarization induced ion transport significantly relies on the enteric glial activity (narrow blue arrow) while glia‐stimulated secretory response is mostly mediated via neurons (thick green arrow) and additional mechanisms that may include direct signaling between enteric glial cells and enterocytes (narrow green arrow).