Please use this identifier to cite or link to this item: https://repositorio.usj.es/handle/123456789/291

Title: KCa3.1 Transgene Induction in Murine Intestinal Epithelium Causes Duodenal Chyme Accumulation and Impairs Duodenal Contractility
Authors: Valero Gracia, Marta Sofía ORCID SCOPUSID
Ramón-Giménez, Mariano ORCID SCOPUSID
Lozano-Gerona, Javier ORCID SCOPUSID
Delgado-Wicke, Pablo ORCID SCOPUSID
Calmarza, Pilar SCOPUSID
Olivan-Viguera, Aida ORCID RESEARCHERID
López Ramos, Víctor
García-Otín, Ángel Luis ORCID RESEARCHERID SCOPUSID
Valero, Salvador
Pueyo, Esther ORCID RESEARCHERID SCOPUSID
Hamilton, Kirk L SCOPUSID
Miura, Hiroto SCOPUSID
Köhler, Ralf ORCID SCOPUSID
Keywords: Intermediate-conductance calcium-activated potassium channel; KCa3.1; Epithelium; Duodenum; Contractility; Transgenic mice
Issue Date: 8-Mar-2019
Citation: Valero, M.S.; Ramón-Gimenez, M.; Lozano-Gerona, J.; Delgado-Wicke, P.; Calmarza, P.; Oliván-Viguera, A.; López, V.; Garcia-Otín, Á.-L.; Valero, S.; Pueyo, E.; Hamilton, K.L.; Miura, H.; Köhler, R. KCa3.1 Transgene Induction in Murine Intestinal Epithelium Causes Duodenal Chyme Accumulation and Impairs Duodenal Contractility. Int. J. Mol. Sci. 2019, 20, 1193.
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.
URI: https://repositorio.usj.es/handle/123456789/291
ISSN: 1422-0067
Appears in Collections:Artículos de revistas

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