ArticleThe Journal of investigative dermatology2015
Aberrant connexin26 hemichannels underlying keratitis-ichthyosis-deafness syndrome are potently inhibited by mefloquine.
Article in The Journal of investigative dermatology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 27 citations in OpenAlex.
- Treatment of Epidermal Pathology in a Pediatric Patient With Keratitis-Ichthyosis-Deafness (KID) Syndrome With Topical Mefenamic Acid.Pediatric dermatology · 2025Article
- The genetic and molecular basis of a connexin-linked skin disease.The Biochemical journal · 2024Review
- Connexins in epidermal health and diseases: insights into their mutations, implications, and therapeutic solutions.Frontiers in physiology · 2024Review
- Cellular mechanisms of connexin-based inherited diseases.Trends in cell biology · 2022Review
- Connexin hemichannel inhibition ameliorates epidermal pathology in a mouse model of keratitis ichthyosis deafness syndrome.Scientific reports · 2021Article
- Mechanisms Underlying Connexin Hemichannel Activation in Disease.International journal of molecular sciences · 2021Review
- Review
- Allele-Specific Small Interfering RNA Corrects Aberrant Cellular Phenotype in Keratitis-Ichthyosis-Deafness Syndrome Keratinocytes.The Journal of investigative dermatology · 2020Article
- Cx26 keratitis ichthyosis deafness syndrome mutations trigger alternative splicing of Cx26 to prevent expression and cause toxicityRoyal Society open science · 2019Article
- Inhibitors of connexin and pannexin channels as potential therapeutics.Pharmacology & therapeutics · 2017Review
- Design and Characterization of a Human Monoclonal Antibody that Modulates Mutant Connexin 26 Hemichannels Implicated in Deafness and Skin Disorders.Frontiers in molecular neuroscience · 2017Article
- Altered CO2 sensitivity of connexin26 mutant hemichannels in vitro.Physiological reports · 2016Article
- Altered cellular localization and hemichannel activities of KID syndrome associated connexin26 I30N and D50Y mutations.BMC cell biology · 2016Article
- Connexin hemichannels influence genetically determined inflammatory and hyperproliferative skin diseases.Pharmacological research · 2015Article
- Erythrokeratodermia variabilis et progressiva allelic to oculo-dento-digital dysplasia.The Journal of investigative dermatology · 2015Article
- The double life of connexin channels: single is a treat.The Journal of investigative dermatology · 2015Article
- Complex Membrane Channel Blockade: A Unifying Hypothesis for the Prodromal and Acute Neuropsychiatric Sequelae Resulting from Exposure to the Antimalarial Drug Mefloquine.Journal of parasitology research · 2015Review
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7 authors at 2 institutions in 1 country.
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Abstract
Keratitis-ichthyosis-deafness (KID) syndrome is an ectodermal dysplasia caused by dominant mutations of connexin26 (Cx26). Loss of Cx26 function causes nonsyndromic sensorineural deafness, without consequence in the epidermis. Functional analyses have revealed that a majority of KID-causing mutations confer a novel expansion of hemichannel activity, mediated by connexin channels in a nonjunctional configuration. Inappropriate Cx26 hemichannel opening is hypothesized to compromise keratinocyte integrity and epidermal homeostasis. Pharmacological modulators of Cx26 are needed to assess the pathomechanistic involvement of hemichannels in the development of hyperkeratosis in KID syndrome. We have used electrophysiological assays to evaluate small-molecule analogs of quinine for suppressive effects on aberrant hemichannel currents elicited by KID mutations. Here, we show that mefloquine (MFQ) inhibits several mutant hemichannel forms implicated in KID syndrome when expressed in Xenopus laevis oocytes (IC50∼16 μM), using an extracellular divalent cation, zinc (Zn(++)), as a nonspecific positive control for comparison (IC50∼3 μM). Furthermore, we used freshly isolated transgenic keratinocytes to show that micromolar concentrations of MFQ attenuated increased macroscopic membrane currents in primary mouse keratinocytes expressing human Cx26-G45E, a mutation that causes a lethal form of KID syndrome.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.