DOWN-REGULATION OF Kir2.6 CHANNEL BY C-TERMINI MUTATION D252N AND ITS ASSOCIATION WITH THE SUSCEPTIBILITY TO THYROTOXIC PERIODIC PARALYSIS

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dc.contributor.author Paninka, Rolf Matias [UNIFESP]
dc.contributor.author Carlos-Lima, Estevao [UNIFESP]
dc.contributor.author Lindsey, Susan C. [UNIFESP]
dc.contributor.author Kunii, Ilda S. [UNIFESP]
dc.contributor.author Dias-Da-Silva, Magnus R. [UNIFESP]
dc.contributor.author Arcisio-Miranda, Manoel [UNIFESP]
dc.date.accessioned 2020-07-17T14:02:37Z
dc.date.available 2020-07-17T14:02:37Z
dc.date.issued 2017
dc.identifier http://dx.doi.org/10.1016/j.neuroscience.2017.01.019
dc.identifier.citation Neuroscience. Oxford, v. 346, p. 197-202, 2017.
dc.identifier.issn 0306-4522
dc.identifier.uri https://repositorio.unifesp.br/handle/11600/54909
dc.description.abstract Inward rectifying potassium - Kir - channels drive the resting potential to potassium reversal potential and, when disrupted, might be related to muscular diseases. Recently, Thyrotoxic Periodic Paralysis (TPP) has emerged as a channelopathy related to mutations in KCNJ18 gene, which encodes Kir2.6 channel. TPP is a neuromuscular disorder characterized by a triad of muscle weakness, hypokalemia, and thyrotoxicosis, the latter being essential for the crisis. Direct sequencing revealed two heterozygous mutations - D252N and R386C - in two TPP patients. KCNJ18 cDNAs were cloned into mammalian expression plasmids and transiently expressed in HEK 293T cells to investigate the functional effects of Kir2.6 mutations. Patch-clamp and confocal laser scanning microscopy experiments were carried out, comparing the WT channel to its mutants. D252N mutation down-regulates the Kir2.6 activity, decreasing the K+ current density (similar to 34%) when compared to the WT channel en
dc.description.abstract whereas the mutation R386C shows no significant changes from WT. The mutant D252N Kir2.6 channel also showed a substantial reduction of similar to 51% in membrane abundance relative to WT channel. Our study describes the functional consequences of a single amino acid change in Kir2.6 channel. Further analysis regarding hormonal conditions and Kir channel expression are required to provide new clues about the TPP pathophysiology. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved. en
dc.description.sponsorship Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (Fapesp)
dc.description.sponsorship Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
dc.format.extent 197-202
dc.language.iso eng
dc.publisher Pergamon-Elsevier Science Ltd
dc.relation.ispartof Neuroscience
dc.rights Acesso restrito
dc.subject Kir channel en
dc.subject Kir2.6 en
dc.subject potassium channel en
dc.subject Thyrotoxic Periodic Paralysis en
dc.title DOWN-REGULATION OF Kir2.6 CHANNEL BY C-TERMINI MUTATION D252N AND ITS ASSOCIATION WITH THE SUSCEPTIBILITY TO THYROTOXIC PERIODIC PARALYSIS en
dc.type Artigo
dc.description.affiliation Univ Fed Sao Paulo, Escola Paulista Med, Dept Biofis, Lab Neurobiol Estrutural Func, Rua Botucatu 862-7 andar, BR-04023060 Sao Paulo, SP, Brazil
dc.description.affiliation Univ Fed Sao Paulo, Escola Paulista Med, Lab Endocrinol Mol Translac, Rua Pedro Toledo 669,11 andar, BR-04039032 Sao Paulo, SP, Brazil
dc.description.affiliationUnifesp Univ Fed Sao Paulo, Escola Paulista Med, Dept Biofis, Lab Neurobiol Estrutural Func, Rua Botucatu 862-7 andar, BR-04023060 Sao Paulo, SP, Brazil
dc.description.affiliationUnifesp Univ Fed Sao Paulo, Escola Paulista Med, Lab Endocrinol Mol Translac, Rua Pedro Toledo 669,11 andar, BR-04039032 Sao Paulo, SP, Brazil
dc.description.sponsorshipID FAPESP: 2010/52077-9
dc.description.sponsorshipID FAPESP: 2011/20747-8
dc.description.sponsorshipID CNPq: 142157/2014-7
dc.identifier.doi 10.1016/j.neuroscience.2017.01.019
dc.description.source Web of Science
dc.identifier.wos WOS:000395790100019
dc.coverage Oxford
dc.citation.volume 346



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