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KCa3.1 Transgene Induction in Murine Intestinal Epithelium Causes Duodenal Chyme Accumulation and Impairs Duodenal Contractility
- Source :
- R-USJ: Repositorio Institucional de la Universidad San Jorge, Universidad San Jorge (USJ), International Journal of Molecular Sciences, Volume 20, Issue 5, Zaguán. Repositorio Digital de la Universidad de Zaragoza, instname, International Journal of Molecular Sciences, Vol 20, Iss 5, p 1193 (2019)
- Publication Year :
- 2019
-
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&minus<br />) 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&minus<br />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.
- Subjects :
- Intermediate-conductance calcium-activated potassium channel
duodenum
Contractility
Epithelium
lcsh:Chemistry
Mice
0302 clinical medicine
Transgenic mice
Transgenes
Intestinal Mucosa
lcsh:QH301-705.5
Spectroscopy
0303 health sciences
TUNEL assay
biology
Chemistry
General Medicine
Intermediate-Conductance Calcium-Activated Potassium Channels
Intestinal epithelium
Up-Regulation
3. Good health
Computer Science Applications
Cell biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
Investigación
Digestion
Muscle Contraction
intermediate-conductance calcium-activated potassium channel
Genetically modified mouse
Duodenum
Transgene
transgenic mice
contractility
Article
Catalysis
Inorganic Chemistry
03 medical and health sciences
medicine
Animals
Physical and Theoretical Chemistry
Molecular Biology
030304 developmental biology
Organic Chemistry
Proliferating cell nuclear antigen
Mice, Inbred C57BL
lcsh:Biology (General)
lcsh:QD1-999
Apoptosis
biology.protein
KCa3.1
epithelium
Gene Deletion
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- R-USJ: Repositorio Institucional de la Universidad San Jorge, Universidad San Jorge (USJ), International Journal of Molecular Sciences, Volume 20, Issue 5, Zaguán. Repositorio Digital de la Universidad de Zaragoza, instname, International Journal of Molecular Sciences, Vol 20, Iss 5, p 1193 (2019)
- Accession number :
- edsair.doi.dedup.....654feadb0b129fd2180918e12ca3cc25