scholarly journals The epithelial potassium channel Kir7.1 is stimulated by progesterone

2021 ◽  
Vol 153 (10) ◽  
Author(s):  
Ida Björkgren ◽  
Sarah Mendoza ◽  
Dong Hwa Chung ◽  
Monika Haoui ◽  
Natalie True Petersen ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Progesterone Receptors ◽  
Current Clamp ◽  
Inwardly Rectifying Potassium Channel ◽  
Whole Cell Patch Clamp ◽  
Inwardly Rectifying ◽  
The Brain ◽  
Precise Molecular Mechanism

The choroid plexus (CP) epithelium secretes cerebrospinal fluid and plays an important role in healthy homeostasis of the brain. CP function can be influenced by sex steroid hormones; however, the precise molecular mechanism of such regulation is not well understood. Here, using whole-cell patch-clamp recordings from male and female murine CP cells, we show that application of progesterone resulted in specific and strong potentiation of the inwardly rectifying potassium channel Kir7.1, an essential protein that is expressed in CP and is required for survival. The potentiation was progesterone specific and independent of other known progesterone receptors expressed in CP. This effect was recapitulated with recombinant Kir7.1, as well as with endogenous Kir7.1 expressed in the retinal pigment epithelium. Current-clamp studies further showed a progesterone-induced hyperpolarization of CP cells. Our results provide evidence of a progesterone-driven control of tissues in which Kir7.1 is present.

scholarly journals G protein–coupled receptors differentially regulate glycosylation and activity of the inwardly rectifying potassium channel Kir7.1

2018 ◽  
Vol 293 (46) ◽  
pp. 17739-17753 ◽  
Author(s):  
Sheridan J. Carrington ◽  
Ciria C. Hernandez ◽  
Daniel R. Swale ◽  
Oluwatosin A. Aluko ◽  
Jerod S. Denton ◽  
...  
Keyword(s):  
Potassium Channel ◽  
G Protein ◽  
Single Channel ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
G Protein Coupled Receptors ◽  
Open Probability ◽  
Inwardly Rectifying Potassium Channel ◽  
Inwardly Rectifying ◽  
G Protein Coupled

Kir7.1 is an inwardly rectifying potassium channel with important roles in the regulation of the membrane potential in retinal pigment epithelium, uterine smooth muscle, and hypothalamic neurons. Regulation of G protein–coupled inwardly rectifying potassium (GIRK) channels by G protein–coupled receptors (GPCRs) via the G protein βγ subunits has been well characterized. However, how Kir channels are regulated is incompletely understood. We report here that Kir7.1 is also regulated by GPCRs, but through a different mechanism. Using Western blotting analysis, we observed that multiple GPCRs tested caused a striking reduction in the complex glycosylation of Kir7.1. Further, GPCR-mediated reduction of Kir7.1 glycosylation in HEK293T cells did not alter its expression at the cell surface but decreased channel activity. Of note, mutagenesis of the sole Kir7.1 glycosylation site reduced conductance and open probability, as indicated by single-channel recording. Additionally, we report that the L241P mutation of Kir7.1 associated with Lebers congenital amaurosis (LCA), an inherited retinal degenerative disease, has significantly reduced complex glycosylation. Collectively, these results suggest that Kir7.1 channel glycosylation is essential for function, and this activity within cells is suppressed by most GPCRs. The melanocortin-4 receptor (MC4R), a GPCR previously reported to induce ligand-regulated activity of this channel, is the only GPCR tested that does not have this effect on Kir7.1.

scholarly journals Metabolism in the Zebrafish Retina

2021 ◽  
Vol 9 (1) ◽  
pp. 10
Author(s):  
Natalia Jaroszynska ◽  
Philippa Harding ◽  
Mariya Moosajee
Keyword(s):  
Pigment Epithelium ◽  
Retinal Pigment ◽  
The Body ◽  
Therapeutic Approaches ◽  
Retinal Photoreceptors ◽  
Sufficient Energy ◽  
Metabolic Products ◽  
Sight Loss ◽  
Choroidal Vasculature ◽  
The Brain

Retinal photoreceptors are amongst the most metabolically active cells in the body, consuming more glucose as a metabolic substrate than even the brain. This ensures that there is sufficient energy to establish and maintain photoreceptor functions during and after their differentiation. Such high dependence on glucose metabolism is conserved across vertebrates, including zebrafish from early larval through to adult retinal stages. As the zebrafish retina develops rapidly, reaching an adult-like structure by 72 hours post fertilisation, zebrafish larvae can be used to study metabolism not only during retinogenesis, but also in functionally mature retinae. The interplay between rod and cone photoreceptors and the neighbouring retinal pigment epithelium (RPE) cells establishes a metabolic ecosystem that provides essential control of their individual functions, overall maintaining healthy vision. The RPE facilitates efficient supply of glucose from the choroidal vasculature to the photoreceptors, which produce metabolic products that in turn fuel RPE metabolism. Many inherited retinal diseases (IRDs) result in photoreceptor degeneration, either directly arising from photoreceptor-specific mutations or secondary to RPE loss, leading to sight loss. Evidence from a number of vertebrate studies suggests that the imbalance of the metabolic ecosystem in the outer retina contributes to metabolic failure and disease pathogenesis. The use of larval zebrafish mutants with disease-specific mutations that mirror those seen in human patients allows us to uncover mechanisms of such dysregulation and disease pathology with progression from embryonic to adult stages, as well as providing a means of testing novel therapeutic approaches.

The inwardly rectifying potassium channel subunit Kir2.2v (KCNJN1) maps to 17p11.2→p11.1

1997 ◽  
Vol 79 (1-2) ◽  
pp. 85-87 ◽  
Author(s):  
N. Namba ◽  
R. Mori ◽  
H. Tanaka ◽  
I. Kondo ◽  
K. Narahara ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Inwardly Rectifying Potassium Channel ◽  
Inwardly Rectifying
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