info:eu-repo/semantics/doctoralThesis
Location and function of Kir7.1 in transporter epithelials
Autor
Villanueva Subiabre, Sandra Paulina
Institución
Resumen
Kir7.1 is an inwardly rectifying potassium-channel encoded by the Kcnj13 gene. It is present in epithelial tissues where it colocalizes with the Na+/K+-ATPase possibly playing a role in recycling K+ and to maintain the membrane potential required for cell function. We used a Kir7.1 knockout mouse expressing β-galactosidase under the control of Kir7.1 promoter and identified the expression of Kir7.1 in non-pigmented ciliary epithelial cells and mouse airways. Using a knockin mouse expressing the Kir7.1 protein tagged with haemagglutinin or Flag epitopes, we observed basolateral expression of Kir7.1 in non-pigmented ciliary epithelial cells, enterocytes in the jejunum-ileum transition, and ciliated airway epithelial cells.
Electrophysiological experiments using a Kir7.1 tissue-specific knockout mouse model demonstrated that Ki7.1 has no role in sodium-coupled glucose uptake in the small intestine.
The ciliary body epithelium (CBE) of the eye is a determinant of intraocular pressure (IOP) through fluid secretion in the aqueous humour. Measurements using the conditional knockout mouse show only a minor effect of Kir7.1 inactivation on steadystate IOP. Transient increases in IOP in response to general anaesthetics, or to water injection, are absent or markedly reduced in Kir7.1-deficient mice. These results suggest a role for Kir7.1 in IOP regulation through possible modulation of aqueous humour production by the CBE non-pigmented epithelial cells.
Genetic silencing and pharmacological inactivation of Kir7.1 in the mouse airways, and primary human bronchial epithelial cell cultures showed that the channel has negligible effects on the transepithelial transport. However, Kir7.1 inactivation modifies the speed and orientation of the mucociliary clearance (MCC). This is the first evidence showing that Kir7.1 has a role in MCC.
Kir7.1 channel is expressed in colocalization with the Na+/K+-ATPase in the intestinal epithelium, the ciliated cells of the respiratory epithelium and in the ciliary body of the eye. In the latter, it appears to be important in the balance of aqueous humor flow thatdetermines IOP, making it a potential target for the development of drugs of use in pathological situations affecting IOP.