KCa3.1 Transgene Induction in Murine Intestinal Epithelium Causes Duodenal Chyme Accumulation and Impairs Duodenal Contractility
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Authors
Valero, Marta S.
Ramon-Gimenez, Mariano
Lozano-Gerona, Javier
Delgado-Wicke, Pablo
Calmarza, Pilar
Olivan-Viguera, Aida
Lopez, Victor S.
Garcia-Otin, Angel-Luis
Valero, Salvador
Pueyo, Esther
Issue Date
2019
Type
Article
Language
Keywords
intermediate-conductance calcium-activated potassium channel , KCa3.1 , epithelium , duodenum , contractility , transgenic mice
Alternative Title
Abstract
The epithelial intermediate-conductance calcium/calmodulin-regulated KCa3.1 channel is considered to be a regulator of intestine function by controlling chloride secretion and water/salt balance. Yet, little is known about the functional importance of KCa3.1 in the intestinal epithelium in vivo. Our objective was to determine the impact of epithelial-specific inducible overexpression of a KCa3.1 transgene (KCa3.1+) and of inducible suppression (KCa3.1-) on intestinal homeostasis and function in mice. KCa3.1 overexpression in the duodenal epithelium of doxycycline (DOX)-treated KCa3.1+ mice was 40-fold above the control levels. Overexpression caused an inflated duodenum and doubling of the chyme content. Histology showed conserved architecture of crypts, villi, and smooth muscle. Unaltered proliferating cell nuclear antigen (PCNA) immune reactivity and reduced amounts of terminal deoxynucleotide transferase mediated X-dUTP nick end labeling (TUNEL)-positive apoptotic cells in villi indicated lower epithelial turnover. Myography showed a reduction in the frequency of spontaneous propulsive muscle contractions with no change in amplitude. The amount of stool in the colon was increased and the frequency of colonic contractions was reduced in KCa3.1+ animals. Senicapoc treatment prevented the phenotype. Suppression of KCa3.1 in DOX-treated KCa3.1- mice caused no overt intestinal phenotype. In conclusion, inducible KCa3.1 overexpression alters intestinal functions by increasing the chyme content and reducing spontaneous contractions and epithelial apoptosis. Induction of epithelial KCa3.1 can play a mechanistic role in the process of adaptation of the intestine.
Description
Citation
Valero, M. S., Ram—n-Gimenez, M., Lozano-Gerona, J., Delgado-Wicke, P., Calmarza, P., Oliv‡n-Viguera, A., É Kšhler, R. (2019). KCa3.1 Transgene Induction in Murine Intestinal Epithelium Causes Duodenal Chyme Accumulation and Impairs Duodenal Contractility. International Journal of Molecular Sciences, 20(5), 1193. doi:10.3390/ijms20051193
Publisher
Journal
Volume
Issue
PubMed ID
ISSN
1422-0067