Molecular Basis of human channelopathies associated to ENaC |
Dra. Teresa Giraldez,
Investigator-Group leader
“Miguel Servet” Program
Our work is focused on the study of the molecular and structural mechanisms implicated in function and regulation of ion channels ENaC (epithelial sodium channel) and BK (ca- and voltage-regulated potassium channel). For this purpose we combine a large variety of molecular biology tecniques, genetics, microscopy, fluorometry and electrophysiology.
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Delta Subunit:
In our lab we study the molecular composition, functional properties and possible physiological roles of voltage-independent sodium channels formed by the epithelial sodium channel (ENaC) delta subunit. This subunit presents atypical characteristics, since unlike classical ENaC subunits, it is expressed in non-epithelial tissues. Moreover, its coding gene is present only in human and primates. We have recently described two new delta ENaC isoforms and their differential expression in pyramidal neurons of the human cortex (Giraldez et al, J Neurochem, in press). Our data suggests that delta forms voltage-independent sodium channels in non epithelial tissues via interaction with other accessory subunits. The identity of these other subunits is unknown. Our aims are: 1) to define subunit composition and stoichiometry of delta ENaC channels in vivo; 2) to study the functional characteristics of each isoform and correlate them with their possible physiological roles; 3) to determine delta ENaC channels subcellular localization in neurons; and 4) to study the stoichiometry of “classic” ENaC channels with fluorescence techniques.
- Conformational Dynamics of BK Channels:
This project studies the structural dynamics of calcium- and voltaje-sensitive potassium channels (BK or slo), focusing on the basis of coupling between calcium and voltaje regulation. To that end I have developed a library of functional fluorescent BK channels with insertions of green fluorescent protein variants (YFP and CFP) in various sites into the channel protein (Giraldez et al 2005, J Gen Physiol 126:429). Co-expression of different combinations of fluorescent channels and the use of patch-clamp fluorometry allows detecting structural rearrangements by changes in FRET efficiency while simultaneously recording electrical activity.
Research Grants
- 2008-2010. Mecanismos moleculares de canalopatías asociadas a los canales de sodio ENaC.
Fondo de Investigación Sanitaria. (CP07/00034)
- 2008-2012 CONSOLIDER SICI (THE SPANISH ION CHANNEL INITIATIVE).
MICINN CSD2008_00005
http://sici.umh.es
- 2009-2011. Acción integrada Hispano-Alemana
MICINN (HD2008-0025)
- 2009-2012 Papel de nuevas subunidades del canal epitelial de sodio (delta-ENaC) en el daño neuronal y la enfermedad de Parkinson.
F.I.S. (ISCIII/MICINN; PS09/00406)
- 2010-2011. Detección de reorganizaciones estructurales del canal iónico humano hslo en tiempo real.
Fundación L’Oreal-UNESCO
- 2010-2011. Generación de un modelo animal para estudiar el papel de la proteína d-ENaC en enfermedades neurodegenerativas.
Fundación Canaria de Investigación y Salud (FUNCIS; PI20/09)
- 2012-2015. Estudio de nuevos mecanismos moleculares implicados en la regulación iónica de la excitabilidad celular subyacentes al daño neuronal y enfermedades neurológicas (PS12/00428).Entidad Financiadora: Fondo de Investigacion Sanitaria (ISCIII/MINECO). Investigadora Principal
- 2012-2014. Illuminating the activation of glutamate receptors with fluorescent probes (Senate Committee Competition (SAW)). Entidad financiadora: Leibniz Association (WGL) (I. P. Andrew Plested, FMP, Berlin, Alemania). Colaboradora
- 2013-2015. IMPROVEMENT OF BIOMEDICAL RESEARCH AND INNOVATION IN THE CANARY ISLANDS (IMBRAIN). Entidad Financiadora: EuropeanUnion (Program identifier: FP7-REGPOT-2012-2013-1) CALL:“Integration of research entities from the EU´s Convergence and Outermost regions in the ERA and enhancement of their innovation potential”. Referencia: 316137 – IMBRAIN. Líder de Grupo e Investigación Participante/Coordinadora de Intercambio Internacional.
- 2012-2013. Dinamización mediante TICs del proceso enseñanza-aprendizaje en Másteres de Ciencias de la Salud. Universidad de La Laguna. Convocatoria competitiva de Proyectos de innovación educativa. Colaboradora. I. P. Guadalberto Hernández (ULL)
- 2013-2015. Adaptaciones evolutivas de canales de potasio dependientes de voltaje en un organismo antártico (RT_15-12). INACH (Chile). Investigador Principal. Patricio Rojas, Universidad Santiago de Chile. Colaboradora.
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