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Francisco Leandro Sepúlveda Valenzuela

Research

CENTRO DE ESTUDIOS CIENTÍFICOS (CECS)

Valdivia, Chile

Líneas de Investigación


Estructura funcion de canales ionicos; Sensores de pH; Fisio(pato)logía epitelial; Fisiologia Celular; Transporte epitelial; Canales de cloruro y potasio de los epitelios; Transepithelial transport; Ionic channels; Intestinal physiology and pathophysiology

Educación

  •  Licenciatura en Ciencias, mención Biología, UNIVERSIDAD DE CHILE. Chile, 1972
  •  Doctor of Science in Biochemistry, Université de Lausanne. Suiza, 1977

Experiencia Académica

  •   Asistente de Investigación Full Time

    UNIVERSIDAD DE CHILE

    Facultad de Ciencias

    Santiago, Chile

    1973 - 1977

  •   Maître de confèrences associé Full Time

    Université de Nice

    Faculté des Sciences

    Nice, Francia

    1978 - 1978

  •   Senior Scientific Officer Full Time

    AFRCInstitute of Animal Physiology and Genetics Research

    Cambridge, Reino Unido

    1979 - 1981

  •   Principal Scientific Full Time

    AFRC Institute of Animal Physiology and Genetics Research

    Cambridge, Reino Unido

    1981 - 1989

  •   Senior Principal - Scientific Officer Full Time

    AFRC Institute of Animal Physiology and Genetics Research

    Cambridge, Reino Unido

    1990 - 1994

  •   Profesor Full Time

    Centro de Estudios Científicos de Santiago

    Santiago, Chile

    1994 - 1999

  •   Profesor ad Honorem Part Time

    UNIVERSIDAD DE CHILE

    Medicina

    Santiago, Chile

    1994 - A la fecha

  •   Research Full Time

    Centro de Estudios Científicos

    Valdivia, Chile

    1999 - A la fecha

  •   Postdoctoral Fellow Full Time

    AFRC Institute of Animal Physiology and Genetics Research

    Cambridge, Reino Unido

    1977 - 1979

Experiencia Profesional

  •   Supervisor in Physiology Part Time

    University of Cambridge

    Cambridge, Reino Unido

    1985 - 1989

  •   External Lecturer Part Time

    Queen Elizabeth College, University de London

    London, Reino Unido

    1981 - 1986

  •   External Lecturer Part Time

    King's College, University de London

    London, Reino Unido

    1987 - 1994

  •   Visiting Professor Part Time

    Université de Paris-6 Pierre et Marie Curie

    Paris, Francia

    2011 - 2016

Formación de Capital Humano


Undergraduate Students:
* Pedro Gallardo, "Regulación del Transporte de agua en colon distal, a Canales de agua aquaporina en colon distal de rata y b. canales de agua aquaporina en rodentes de desierto del norte de Chile, absorción de agua co". Ponticificia Universidad Católica de Chile. Finished 2008.
* Francisca Andrea Julio Kalajzic, "Papel de los canales basolaterales de potasio en la secreción intestinal de cloruro". Undergraduate Biochemist. Pontificia Universidad Católica de Valparaiso. Finished 2014.
* Néstor Bastián Corro Acuña. "Mecanismo de acción del bloqueador Tetra-Pentil-Amonio en el canal de potasio TASK-2". Undergraduate Biochemist. Universidad Austral de Chile. Finished in 2014.
* Erwin Leonel Vera Pinilla. "Papel del canal de potasio Kir7.1 en el epitelio intestinal". Undergraduate Medical Technologist. Universidad Austral de Chile. Finished 2017.

PhD Student:
* Leandro Antonio Zúñiga Hormazábal, "Analisis molecular del mecanismo de inhibicion por protones en los canales de potasio pertenecientes a la subfamila TASK", Doctor of Science. Universidad Austral de Chile. Finished 2008.
* Gaspar Peña Münzenmayer. "Mecanismo de Regulación del Canal de Potasio Task-2 por Variaciones del ph Intracelular". Cellular and Molecular Biology PhD. Universidad Austral de Chile. Finished in 2011.
* Viviana Angélica Bustos Salgado. "Regulación del canal de potasio KCNQ1:KCNE3 por 17 beta-estradiol". Cellular and Molecular Biology PhD. Universidad Austral de Chile. Finished in 2012.
* Johana Lisbeth Burgos Vargas. " ". Cellular and Molecular Biology PhD. Universidad Austral de Chile. Ongoing.
* Sandra Paulina Villanueva Subiabre. " Rol del canal de potasio Kir7.1 en el transporte transepitelial de las vías aéreas" Cellular and Molecular Biology PhD. Universidad Austral de Chile. Ongoing.


Difusión y Transferencia


Membership
* Physiological Society (UK)
* Sociedad de Biología de Chile
* Sociedad Chilena de Ciencias Fisiológicas
* Sociedad Chilena de Bioquímica y Biología Celular
* American Society of Biochemistry and Molecular Biology

Collaborative Activities
* Course Science and Poetry, "Células Madre: Ciencia y P...romesa", Universidad Austral de Chile, 31th May 2016, Valdivia, Chile.
* Course Science and Poetry, "Células Madre: Ciencia y Promesa", Universidad Austral de Chile, 16th May 2017, Valdivia, Chile.

Visit in Chile
* Working meetings, Dr. Dominique Eladari, Centre de Recherche des Cordeliers Unité INSERM U872, Equipe 3 Escalier E-RDC, Paris, 22th January to 01st Febraury 2013.
* Working meetings, Dra. Andrea González, MedImmune, Cambridge, 22 th January 2013.
* Working meetings, Dra. Gloria Riquelme, Facultad de Medicina y Jefa de gabinete del Rector, Universidad de Chile, 05th Febraury 2013.
* Working meetings, Michael Janta, Universidad Würzburg, Alemania, 23th January 2013.
* Working meetings, Wendy González, Universidad de Talca, 24th January 2013.
* Working meetings, Andrea Peruffo, Tecniplast, 24th - 26th January 2013.
* Working meetings, Graciela Gigola, Universidad Nacional del Sur, 24th - 26th January 2013.
* Working meetings, Dasha Fuentes, Centro Nacional para la Producción de Animales de Laboratorio (CENPALAB), 24th - 26th January 2013.
* Colloquium, Dr. Yaroslav Ispolatov, Departamento de Física, Facultad de Ciencia Universidad de Santiago de Chile, 07th november 2013
* Working meetings, Dr. Jacques Teulon, Universite Pierre et Marie Curie-Paris 6, Paris, 25th - 30th November 2013.
* Collaborative scientific meeting with Dr. Jacques Teulon, Universidad Pierre et marie Curie, Paris, 09th - 31th January 2017.

Visit Abroad
* Collaborative scientific meeting with Dr. Dominique Eladari y Dra. Regine Chambrey, Institut national de la santé et de la recherche médicale, Paris, May 2013.
* Collaborative scientific meeting of Sandra Villanueva with Dr. Jacques Teulon to learn new techniques, Université Pierre et Marie Curie, Paris, 01st May to 01st June 2013.
* Collaborative scientific meeting with Dr. Jacques Teulon, Institut national de la santé et de la recherche médicale, Paris, 19th May to 13th June 2014.
* Collaborative scientific meeting with Dra. Olga Andrini and Dr. Marc Paulais, Universidad Pierre et marie Curie, Paris, 19th May to 13th June 2014.
* Collaborative scientific meeting with Dr. Jacques Teulon, Universidad Pierre et marie Curie, Paris, 01st - 28th July 2015.
* Collaborative scientific meeting with Dr. Jacques Teulon, Universidad Pierre et marie Curie, Paris, 09th - 31th January 2017.


Premios y Distinciones

  •   Zyma, Nyon Studentship

    Nyon University

    Suiza, 1974

    Scholarship obtained to study PhD in science at the University of Lausanne, Switzerland

  •   Fellowship del Fonds National suisse de la recherche scientifique y la Royal Society

    Royal Society

    Reino Unido, 1977

    Fellowship del Fonds National suisse de la recherche scientifique y la Royal Society, Suiza-UK.

  •   Individual Merit promotion

    AFRC Institute of Animal Physiology and Genetics Research

    Reino Unido, 1990

    .

  •   Cátedra Presidencial en Ciencia

    .

    Chile, 1996

    .

  •   Medalla Rectoral

    UNIVERSIDAD DE CHILE

    Chile, 1996

    .

  •   Howard Hughes Medical Institute International Scholarhip

    Howard Hughes Medical Institute International

    Estados Unidos, 1997

    .

  •   John Simon Guggenheim Memorial Foundation Fellowship

    John Simon Guggenheim Memorial Foundation

    Estados Unidos, 2001

    .

  •   Senior Editor

    The Journal of Physiology

    Reino Unido, 2016

    .


 

Article (46)

Chloride goes through TMEM16A channels with permission from Ca2+ and encouragement from protons
Phosphatidylinositol (4,5)bisphosphate dynamically regulates the K-2P background K+ channel TASK-2
Side Fenestrations Provide an "Anchor" for a Stable Binding of A1899 to the Pore of TASK-1 Potassium Channels
Gating, Regulation, and Structure in K2P K+ Channels: In Varietate Concordia?
Channel-Mediated Lactate Release by K+-Stimulated Astrocytes
Cleft Palate, Moderate Lung Developmental Retardation and Early Postnatal Lethality in Mice Deficient in the Kir7.1 Inwardly Rectifying K+ Channel
CLCNKB mutations causing mild Bartter syndrome profoundly alter the pH and Ca2+ dependence of ClC-Kb channels
Zebrafish and mouse TASK-2 K+ channels are inhibited by increased CO2 and intracellular acidification
An Extracellular Ion Pathway Plays a Central Role in the Cooperative Gating of a K-2P K+ Channel by Extracellular pH
Electrophysiological evidence for the presence of cystic fibrosis transmembrane conductance regulator (CFTR) in mouse sperm
G protein modulation of K-2P potassium channel TASK-2
Novel CLCNKB Mutations Causing Bartter Syndrome Affect Channel Surface Expression
Oestrogen promotes KCNQ1 potassium channel endocytosis and postendocytic trafficking in colonic epithelium
Severe Defects in Absorptive Ion Transport in Distal Colons of Mice That Lack ClC-2 Channels
Extracellular pH in Restricted Domains as a Gating Signal for Ion Channels Involved in Transepithelial Transport
Gating of a pH-Sensitive K-2P Potassium Channel by an Electrostatic Effect of Basic Sensor Residues on the Selectivity Filter
Sexual dimorphism and oestrogen regulation of KCNE3 expression modulates the functional properties of KCNQ1 K+ channels
Isolation of the Atlantic salmon beta-actin promoter and its use to drive expression in salmon cells in culture and in transgenic zebrafish
Separate Gating Mechanisms Mediate the Regulation of K-2P Potassium Channel TASK-2 by Intra- and Extracellular pH
Strain-dependent differences in electrogenic secretion of electrolytes across mouse colon epithelium
Rapid Recycling of ClC-2 Chloride Channels Between Plasma Membrane and Endosomes: Role of a Tyrosine Endocytosis Motif in Surface Retrieval
Voltage-dependent and -independent titration of specific residues accounts for complex gating of a ClC chloride channel by extracellular protons
A genetically encoded ratiometric sensor to measure extracellular pH in microdomains bounded by basolateral membranes of epithelial cells
Clcn2 encodes the hyperpolarization-activated chloride channel in the ducts of mouse salivary glands
Abolition of Ca2+-mediated intestinal anion secretion and increased stool dehydration in mice lacking the intermediate conductance Ca2+-dependent K+ channel Kcnn4
Neutralization of a single arginine residue gates open a two-pore domain, alkali-activated K+ channel
Gating of two-pore domain K+ channels by extracellular pH
Removal of gating in voltage-dependent ClC-2 chloride channel by point mutations affecting the pore and C-terminus CBS-2 domain
Two splice variants derived from a Drosophila melanogaster candidate ClC gene generate ClC-2-type Cl(-) channels
Basolateral localization of native ClC-2 chloride channels in absorptive intestinal epithelial cells and basolateral sorting encoded by a CBS-2 domain di-leucine motif
Functional evaluation of human ClC-2 chloride channel mutations associated with idiopathic generalized epilepsies
The voltage-dependent CIC-2 chloride channel has a dual gating mechanism
A conserved pore-lining glutamate as a voltage- and chloride-dependent gate in the CIC-2 chloride channel
Extracellular conserved cysteine forms an intersubunit disulphide bridge in the KCNK5 (TASK-2) K+ channel without having an essential effect upon activity
A voltage-independent K+ conductance activated by cell swelling in Ehrlich cells is modulated by a G-protein-mediated process
ClC-2 in guinea pig colon: mRNA, immunolabeling, and functional evidence for surface epithelium localization
Distribution of aquaporins in the colon of Octodon degus, a South American desert rodent
Effect of an N-terminus deletion on voltage-dependent gating of the ClC-2 chloride channel
Aquaporin-2, a regulated water channel, is expressed in apical membranes of rat distal colon epithelium
Cloning, cellular distribution and functional expression of small intestinal epithelium guinea pig C1C-5 chloride channel
K+ conductance activated during regulatory volume decrease. The channels in Ehrlich cells and their possible molecular counterpart
Modulation of the two-pore domain acid-sensitive K+ channel TASK-2 (KCNK5) by changes in cell volume
Characterisation of a cell swelling-activated K+-selective conductance of Ehrlich mouse ascites tumour cells
K+ currents activated by leukotriene D-4 or osmotic swelling in Ehrlich ascites tumour cells
Splice variants of a ClC-2 chloride channel with differing functional characteristics
Swelling-induced taurine efflux from hela cells: Cell volume regulation

ConferencePoster (2)

Side Fenestrations Provide an “Anchor” for a Stable Binding of A1899 to the Pore of TASK-1 Potassium Channels
Phosphatidylinositol (4,5)-bisphosphate dynamically regulates the K2P background K+ channel TASK-2

ConferenceProceedingWhole (4)

“ TASK%2 two%pore%domain K + channel: thoughts about gating and its fitness to physiological function. ”
Gating and function of TASK-2 channels
Ion channels in intestinal secretion: Physiological insights from mutagenesis
“TASK-2 K2P channel: multiple gating regulators in search of physiological functions.”

EditorialMaterial (2)

B lymphocytes taken to task: a role for a background conductance K-2P K+ channel in B cells. Focus on "Expression of TASK-2 and its upregulation by B cell receptor stimulation in WEHI-231 mouse immature B cells"
A tale from the Crypt: splice variants of BK channels in colonic potassium secretion

Letter (1)

No evidence for a role of CLCN2 variants in idiopathic generalized epilepsy

Proyecto (22)

CLONAMIENTO Y EXPRESION FUNCIONAL DE CANALES DE CLORURO CLC DEL EPITELIO INTESTINAL
CANALES DE CLORURO ACTIVADOS POR CALCIO EN EL EPITELIO INTESTINAL COMO MEDIADORES DE LA SECRECION DE FLUIDO: POTENCIALES MEDIADORES DE LA DIARREA ROTAVIRAL Y MODIFICADORES DEL DEFECTO INTESTINAL EN LA FIBROSIS QUISTICA
DESARROLLO DE UN MODELO CELULAR EXPERIMENTAL PARA LA FIBROSIS QUISTICA (FQ). ESTUDIOS GENETICOS-MOLECULARES Y ELECTROFISIOPATOLOGICOS
EPILEPSIA IDIOPATICA GENERALIZADA: ESTUDIO FUNCIONAL DE MUTACIONES EN EL GEN CLCN2.
ESTUDIO CELULAR Y MOLECULAR D LA VIA BASOLATERAL DE SALIDA DE CLORURO EN EL EPITELIO INTESTINAL
EXPLORING THE POSSIBLE ROLE OF THE INWARDLY RECTIFYING K+ CHANNEL KIR7.1 IN THE CILIATED EPITHELIA OF THE CHOROID PLEXUS AND THE CILIARY BODY OF THE EYE
EXTRACELLULAR AND INTRACELLULAR SENSORS IN THE GATING OF TASK-2, A TWO-PORE-DOMAIN POTASSIUM CHANNEL.
GENERACION DE UN RATON QUE EXPRESE EL CANAL CIC-2 UNIDO A LA PROTEINA FLUORESCENTE VERDE. ESTUDIO DE LOCALIZACION E IMPLICACIONES FUNCIONALES.
IDENTIFICACION MOLECULAR Y CARACTERIZACION FUNCIONAL DEL CANAL DE K EPITELLIAL ACTIVADO POR AUMENTO DEL VOLUMEN CELULAR.
IDENTIFICATION OF POTASSIUM CHANNELS INVOLVED IN SODIUM-COUPLED ABSORPTION NUTRIENTS AND IN THE SECRETION OF ELECTROLYTES AND FLUID IN INTESTINAL EPITHELIUM
MECANISMO DE REGULACION Y ESTRUCTURA OLIGOMERICA DE UN CANAL DE CLORURO EXPRESADO EN EPITELIOS
MECANISMOS MOLECULARES DEL EFECTO DUAL DE LOS PROTONES EXTRACELULARES SOBRE EL GATING DEL CANAL DE CLORURO CLC-2.
MICRODOMINIOS TISULARES DE PH EXTRACELULAR ESTUDIADOS IN SITU CON SU SENSOR CODIFICADO GENETICAMENTE EN RATONES.
MOLECULAR DISSECTION TO STUDY THE CONTRIBUTION OF THE INTRA AND EXTRACELLULAR PH SENSORS OF TASK-2 CHANNELS ON ITS RENAL FUNCTION. AN EXPERIMENTAL APPROACH USING TRANSGENIC MICE TO RESCUE THE TASK-2-NULL PHENOTYPE.
MOLECULAR MECHANISM OF REGULATION OF KCNQ1/KCNE3 POTASSIUM CHANNEL BY 17BETA-OESTRADIOL
PAPEL DE LOS CANALES EPITELIALES DE LA FAMILIA C1C EN LA FUNCION INTESTINAL.
PAPEL DEL CANAL HCLC-2 EN LA GENERACION DE LAS CORRIENTES DE CLORURO RESPONSABLES DE LA REGULACION DEL VOLUMEN EN CELULAS DE MAMIFERO
PARTICIPACION DE TASK-2, UN CANAL DE K+ SENSIBLE A PH EXTRACELULAR, EN LA DISMINUCION DE VOLUMEN CELULAR HOMEOSTATICO Y APOPTOTICO.
PH INDUCED CONFORMATIONAL CHANGES OF CLC CHLORIDE CHANNELS
REGULACION DEL TRANSPORTE DE AGUA EN EL COLON
REGULACION DEL VOLUMEN CELULAR EN CELULAS HELA. PAPEL DE LOS CANALES DE POTASIO Y DEL CALCIO INTRACELULAR
VIAS DE PERMEACION REGULADAS POR EL VOLUMEN CELULAR PARA EL CLORURO Y OSMOLITOS ORGANICOS EN CELULAS HELA. MODULACION POR EL ANION PERMEANTE

Review (6)

K-2P channels in plants and animals
MOLECULAR ASPECTS OF STRUCTURE, GATING, AND PHYSIOLOGY OF pH-SENSITIVE BACKGROUND K-2P AND Kir K+-TRANSPORT CHANNELS
TASK-2 K-2P K+ channel: thoughts about gating and its fitness to physiological function
TASK-2: a K-2p K+ channel with complex regulation and diverse physiological functions
ClC-5 mutations associated with Dent's disease: a major role of the dimer interface
TMEM16 proteins: the long awaited calcium-activated chloride channels?
83
Francisco Sepúlveda

Research

Laboratorio Biología Molecular

CENTRO DE ESTUDIOS CIENTÍFICOS (CECS)

Valdivia, Chile

38
Luis Cid

Principal Research

Laboratorio Biología Molecular

CENTRO DE ESTUDIOS CIENTIFICOS CECs

Valdivia, Chile

34
Maria Niemeyer

Research

Laboratorio Biología Molecular

CENTRO DE ESTUDIOS CIENTIFICOS CECS

Valdivia, Chile

11
Leandro Zuñiga

Profesor Asociado

Medicine

Universidad de Talca

Talca, Chile

9
Carlos Flores

Researcher

Biology Lab

CENTRO DE ESTUDIOS CIENTÍFICOS (CECS)

Valdivia, Chile

8
Wendy Gonzalez

Director of the Center for Bioinformatics, Simulations and Modeling (CBSM)

Bioinformática

CENTRO DE BIOINFORMÁTICA Y SIMULACIÓN MOLECULAR (CBSM)/ UNIVERSIDAD DE TALCA

Talca, Chile

7
Marcelo Catalan

Profesor Auxiliar

Facultad de Medicina

Universidad Austral de Chile

Valdivia, Chile

6
Carlos Figueroa

Head

Anatomy, Histology and Pathology

Universidad Austral de Chile

Valdivia, Chile

5
Isabel Cornejo

Investigadora

Biología

Centro de Estudios Científicos

Valdivia, Chile

3
Andres Stutzin

Full Professor

ICBM

FACULTAD DE MEDICINA UNIVERSIDAD DE CHILE

Santiago, Chile

3
Johanna Burgos

Postdoctoral

Biología

Centro de Estudios Científicos

Valdivia, Chile

3
Fernando Gonzalez

Titular Professor

Facultad de Ciencias de la Vida

Universidad Andres Bello

Santiago, Chile

3
Luis Barros

Principal Research

Laboratorio Biología Molecular

CENTRO DE ESTUDIOS CIENTÍFICOS

Valdivia, Chile

2
Diego Varela

Profesor Asociado

Fisiología y Biofísica

FACULTAD DE MEDICINA, UNIVERSIDAD DE CHILE

Santiago, Chile

2
Bárbara Arévalo

Investigador

Investigación

Centro de Estudios de Alimentos Procesados

Talca, Chile

2
David Ramirez

Profesor Asistente

Facultad de Ciencias de la Salud

Universidad Autónoma de Chile

Santiago, Chile

2
Moisés Sandoval

Co-Investigador

Bioquímica y Microbiología

Universidad Austral de Chile

Valdivia, Chile

1
CAROLINA AÑAZCO

Associate Professor

Preclinical Sciences

Universidad Católica del Maule

TALCA, Chile

1
Ingo Dreyer

Professor Titular

Bioinformatica

Universidad de Talca

Talca, Chile

1
Carlos Vio

Profesor

Fisiologia

PONTIFICIA UNIVERSIDAD CATÓLICA DE CHILE

Santiago, Chile

1
Alejandro San Martin

Senior Reseacher

Biología

CENTRO DE ESTUDIOS CIENTIFICOS

Valdivia, Chile

1
Julio Caballero

Full Professor

Departamento de Bioinformática

Universidad de Talca

Talca, Chile

1
Dulce Figueiras

Investigador responsable

Medicina

Universidad de La Frontera

Temuco, Chile

1
Braulio Valdebenito

.

.

.

TALCA, Chile

1
Gaspar Peña

Profesor Asistente

Instituto de Bioquímica y Microbiología

Universidad Austral de Chile

Valdivia, Chile

1
VALERIA MARQUEZ

Profesor Asistente

Centro de Nanotecnologia Aplicada

Universidad Mayor de Chile

SANTIAGO, Chile

1
Rodrigo Alzamora

ASSISTANT PROFESSOR

INSTITUTE OF BIOMEDICAL SCIENCES

UNIVERSIDAD DE CHILE

Santiago, Chile

1
Sandra Villanueva

Tesista

Biología

Centro de Estudios Científicos

Valdivia, Chile

1
Gonzalo Riadi

Assistant Professor

Bioinformatics

Universidad de Talca

Talca, Chile

1
Viviana Bustos

Researcher

Universidad de Los Lagos

Valdivia, Chile