Abnormal Electroretinogram after Kir7.1 Channel Suppression Suggests Role in Retinal Electrophysiology
| Autor: | Bryce Aul, De-Ann M. Pillers, Andrea Moyer, Pawan K Shahi, Bikash R. Pattnaik, Akshita Pattnaik, Xinling Liu, Jerod S. Denton |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine genetic structures Abnormal electroretinogram Fluorescent Antibody Technique Gene Expression lcsh:Medicine CHO Cells Biology Models Biological Retina Article Mice 03 medical and health sciences chemistry.chemical_compound Cricetulus Electroretinography medicine Animals Potassium Channels Inwardly Rectifying RNA Small Interfering lcsh:Science Multidisciplinary Retinal pigment epithelium lcsh:R Depolarization Retinal Anatomy Hyperpolarization (biology) Immunohistochemistry Photoreceptor outer segment eye diseases Cell biology 030104 developmental biology medicine.anatomical_structure chemistry Female lcsh:Q sense organs Ion Channel Gating Erg Tomography Optical Coherence Photoreceptor Cells Vertebrate |
| Zdroj: | Scientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | The KCNJ13 gene encodes the inwardly rectifying potassium channel, Kir7.1. Mutations in this gene cause childhood blindness, in which the a- and b-wave responses of electroretinogram (ERG) are abolished. The ERG a-wave is the light-induced hyperpolarization of retinal photoreceptors, and the b-wave is the depolarization of ON-bipolar cells. The Kir7.1 channel is localized to the apical aspects of retinal pigment epithelium (RPE) cells and contributes to a delayed c-wave response. We sought to understand why a defect in an RPE ion-channel result in abnormal electrophysiology at the level of the retinal neurons. We have established the expression of Kir7.1 channels in the mouse RPE. ERGs recorded after mice Kir7.1 suppression by shRNA, or by blocking with VU590, showed reduced a-, b- and c-wave amplitudes. In contrast, the Kir7.1 blocker had no effect on the ex-vivo isolated mouse retina ERG where the RPE is not attached to the isolated retina preparation. Finally, we confirmed the specificity of VU590 action by inhibition of native mouse RPE Kir7.1 current in patch-clamp experiment. We propose that mutant RPE Kir7.1 channels contribute directly to the abnormal ERG associated with blindness via alterations in sub-retinal space K+ homeostasis in the vicinity of the photoreceptor outer segment. |
| Databáze: | OpenAIRE |
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