Κυριακή 8 Ιανουαρίου 2017

Enteric glial activity regulates secretomotor function in the mouse colon but does not acutely affect gut permeability

Abstract

Enteric glial cells are often 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::CreERT2+/−/Cx43f/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::CreERT2+/−/Cx43f/f mice significantly reduced neurogenic ion transport. 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 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::CreERT2+/−/Cx43f/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, glial activity does not appear to play a major role in the acute regulation of barrier function. These findings provide novel insight into the cellular mechanisms that control fluid transport homeostasis in the intestine.

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