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dc.contributor.authorIzquierdo García, Carolina-
dc.contributor.authorPeraza, Diego A.-
dc.contributor.authorCercós, Pilar-
dc.contributor.authorMiaja, Pablo-
dc.contributor.authorMerinero, Yaiza G.-
dc.contributor.authorLagartera, L.-
dc.contributor.authorSocuéllamos, Paula G.-
dc.contributor.authorMartín-Martínez, Mercedes-
dc.contributor.authorOlivos-Oré, Luis Alcides-
dc.contributor.authorNaranjo, José Ramón-
dc.contributor.authorArtalejo, Antonio R.-
dc.contributor.authorValenzuela, Carmen-
dc.contributor.authorGutiérrez-Rodríguez, Marta-
dc.identifier.citation19th Meeting SEQT (2019)-
dc.descriptionTrabajo presentado en el 19th Meeting SEQT, celebrado en Vitoria-Gasteiz (España) del 8 al 11 de julio de 2019.-
dc.description.abstractDREAM (Downstream Regulatory Element Antagonist Modulator), also known as KChIP-3 or calsenilin, is a multifunctional calcium binding protein that controls the expression level and/or the activity of several proteins related to calcium homeostasis, neuronal excitability and neuronal survival. As an auxiliary protein in the plasma membrane, DREAM interacts with KV4 potassium channels, L- and T-type voltage-dependent calcium channels, NMDA receptors, presenilins and the transcriptor factor ATF6.1 The interaction between DREAM and KV4 potassium channels regulates of A-type outward potassium currents (IA) that is responsible of the fast repolarization of neuron action potentials and frequency of firing.2 Using a multidisciplinary approach that involves drug design, organic chemistry, surface plasmon resonance assays, electrophysiological recordings of KV4.3/DREAM channels, and IA recordings in rat dorsal root ganglion neurons, we have identified IQM-266.3 IQM-266 slows the inactivation kinetics, and this effect may explain why at concentrations lower than the IC50, IQM-266 augments the efflux of potassium ions resulting in an increase of the charge (activating effect). This effect could be the basis of a promising therapeutic strategy for the treatment of certain neuronal pathologies (epilepsy, Alzheimer disease or ataxia), in which a downregulation of KV4.3 or DREAM has been demonstrated.4 IQM-266 also modulated IA from rat DRG neurons. Overall, IQM-266 constitutes a novel small chemical tool suitable to modulate KV4.3 channels in native systems, that might allow a better understanding of DREAM physiological roles, as well as modulation of neuronal IA current in pathological processes.-
dc.titleChemical tolls to modulate kchip3 signaling-
dc.typecomunicación de congreso-
item.fulltextNo Fulltext-
item.openairetypecomunicación de congreso-
Appears in Collections:(IIBM) Comunicaciones congresos
(IQM) Comunicaciones congresos
(CNB) Comunicaciones congresos
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