Please use this identifier to cite or link to this item:
https://www.um.edu.mt/library/oar/handle/123456789/28245
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Imbrici, Paola | - |
dc.contributor.author | D'Adamo, Maria Cristina | - |
dc.contributor.author | Grottesi, Alessandro | - |
dc.contributor.author | Biscarini, Andrea | - |
dc.contributor.author | Pessia, Mauro | - |
dc.date.accessioned | 2018-03-26T09:54:09Z | - |
dc.date.available | 2018-03-26T09:54:09Z | - |
dc.date.issued | 2011 | - |
dc.identifier.citation | Imbrici, P., D'Adamo, M. C., Grottesi, A., Biscarini, A., & Pessia, M. (2011). Episodic ataxia type 1 mutations affect fast inactivation of K + channels by a reduction in either subunit surface expression or affinity for inactivation domain. American Journal of Physiology - Cell Physiology, 300(6), C1314-C1322. | en_GB |
dc.identifier.uri | https://www.um.edu.mt/library/oar//handle/123456789/28245 | - |
dc.description.abstract | Episodic ataxia type 1 (EA1) is an autosomal dominant disorder characterized by continuous myokymia and episodic attacks of ataxia. Mutations in the gene KCNA1 that encodes the voltage-gated potassium channel Kv1.1 are responsible for EA1. In several brain areas, Kv1.1 coassembles with Kv1.4, which confers N-type inactivating properties to heteromeric channels. It is therefore likely that the rate of inactivation will be determined by the number of Kv1.4 inactivation particles, as set by the precise subunit stoichiometry. We propose that EA1 mutations affect the rate of N-type inactivation either by reduced subunit surface expression, giving rise to a reduced number of Kv1.1 subunits in heterotetramer Kv1.1-Kv1.4 channels, or by reduced affinity for the Kv1.4 inactivation domain. To test this hypothesis, quantified amounts of mRNA for Kv1.4 or Kv1.1 containing selected EA1 mutations either in the inner vestibule of Kv1.1 on S6 or in the transmembrane regions were injected into Xenopus laevis oocytes and the relative rates of inactivation and stoichiometry were determined. The S6 mutations, V404I and V408A, which had normal surface expression, reduced the rate of inactivation by a decreased affinity for the inactivation domain while the mutations I177N in S1 and E325D in S5, which had reduced subunit surface expression, increased the rate of N-type inactivation due to a stoichiometric increase in the number of Kv1.4 subunits. | en_GB |
dc.language.iso | en | en_GB |
dc.publisher | The American Physiological Society | en_GB |
dc.rights | info:eu-repo/semantics/restrictedAccess | en_GB |
dc.subject | Ataxia | en_GB |
dc.subject | Potassium channels | en_GB |
dc.subject | Xenopus laevis | en_GB |
dc.subject | Stoichiometry | en_GB |
dc.title | Episodic ataxia type 1 mutations affect fast inactivation of K + channels by a reduction in either subunit surface expression or affinity for inactivation domain | en_GB |
dc.type | article | en_GB |
dc.rights.holder | The copyright of this work belongs to the author(s)/publisher. The rights of this work are as defined by the appropriate Copyright Legislation or as modified by any successive legislation. Users may access this work and can make use of the information contained in accordance with the Copyright Legislation provided that the author must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the prior permission of the copyright holder. | en_GB |
dc.description.reviewed | peer-reviewed | en_GB |
dc.identifier.doi | 10.1152/ajpcell.00456.2010 | - |
dc.publication.title | American Journal of Physiology - Cell Physiology | en_GB |
Appears in Collections: | Scholarly Works - FacM&SPB |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Episodic_ataxia_type_1_mutations_affect_fast_inact.pdf Restricted Access | 1.16 MB | Adobe PDF | View/Open Request a copy |
Items in OAR@UM are protected by copyright, with all rights reserved, unless otherwise indicated.