Neurophysiology. PI: Xavier Gasull Casanova

Presentation

Within the field of neurophysiology, the group is interested in establishing the role of different ion channels implicated in shaping the excitability of sensory neurons of the dorsal root and trigeminal ganglia, and determining which alterations occur during injury, inflammatory and neuropathic pain states. We are especially interested on ocular pain after inflammation, injury or dry eye disease. On the other hand, in trabecular cells that regulate aqueous humor flow in the eye and intraocular pressure, we are exploring the role of neural mechanisms regulating intraocular pressure and ion K+ and Cl– channels that regulate contraction, shape and cell volume and how this is related to the physiopathology of glaucoma.

Another research area of the group is glutamatergic signaling. This research is mainly focused on the study of the functional interaction between AMPARs and auxiliary subunits and other interacting proteins, which determine this glutamate receptor function at the synapse. On that basis, by means of molecular, cellular and electrophysiological techniques the laboratory is characterizing these functional changes (on gating and trafficking properties) and trying to understand the molecular mechanisms involved in such modulatory effects in heterologous systems, neuronal cultures and slices (hippocampal, cortical). Furthermore, the group is also focused on functional studies on NMDARs with newly synthesized blocking compounds and positive allosteric modulators in the framework of neurodevelopmental conditions.

Xavier Gasull Casanova
Full professor
xgasull@ub.edu

Arcadi Gual Sala
Full professor
agual@ub.edu

Jordi Palés Argullos
Full professor
jpales@ub.edu

Nuria Comes Beltran
Assistant professor
nuriacomes@ub.edu

David Soto del Cerro
Assistant professor
davidsoto@ub.edu

Gerard Callejo Martin
Assistant professor
gerard.callejo@ub.edu

Esther Gratacòs Batlle
Postdoctoral researcher
egratacosbatlle@ub.edu

Belen Mezquita Plà
Assistant professor
belenmezquita@ub.edu

Alba Andrés Bilbé

PhD student
alba.andres4@gmail.com

Roberto García Díaz
PhD student
rogarciadi@unal.edu.co

Andreea Larisa Turcu
PhD student
andreealarisa.turcu@gmail.com

Anna Pujol Coma
PhD student
annapujolcoma@gmail.com

Montserrat Pau Ramon
Administrative and technical staff
montsepau@ub.edu

Federico Miguez Cabello
Research Technician
fj.miguez3@gmail.com

Anna Priscil·la Perez-Gonzalez
Research Technician
apriscil.laperez@ub.edu

  • Physiology and physiopathology of inflammatory and neuropathic pain. Study of ion channels involved in neuronal excitability in the sensory nervous system.
  • Physiology of aqueous humour drainage and physiopathology of glaucoma. Ocular pathology in aging. Physiology of the cells of the ocular trabecular meshwork. Physiopathology of dry eye.
  • Trafficking and regulation of K+ and Cl– channels in cellular physiology. Interaction with membrane proteins and lipids.
  • Glutamatergic signalling: functional interaction between AMPARs and auxiliary subunits and other interacting proteins.
  • NMDAR pharmacology and function in mutations related with neurological conditions.

  • Estudio funcional del proteoma de los receptores AMPA

PI: David Soto del Cerro
MINECO – Ministerio de Economía y Competitividad
BFU2017-83317-P
133.100,00€
2018-2020

  • Bases neurofisiopatológicas del picor y dolor crónico: canales iónicos en neuronas sensoriales implicados en enfermedades inflamatorias y oculares

PI: Xavier Gasull
Fondo de Investigaciones Sanitarias del Instituto de Salud Carlos III
PI17/00296
01/01/2018-31/12/2020

  • Laboratori de Neurofisiologia (grup consolidat)

IP: Xavier Gasull
Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR)
2017_SGR_737
01/01/2017-31/12/2020

  • RETIC Oftared: Prevención, detección precoz, tratamiento y rehabilitación de las patologías oculares

PI: Xavier Gasull
Instituto de Salud Carlos III
RD16/0008/0014
01/01/2017 - 31/12/2021

  • Bases fisiopatológicas del dolor crónico: foco en enfermedades inflamatorias crónicas de la superficie ocular

PI: Xavier Gasull
Fondo de Investigaciones Sanitarias del Instituto de Salud Carlos III
PI14/00141
01/01/2015-31/12/2017

  • Modulación de receptores AMPA por CPT1C: papel en la fisiología neuronal

PI: David Soto
Ministerio de Economía y Competitividad
BFU2014-57562-P
01/01/2015-31/12/2017

  • Laboratori de Neurofisiologia (grup consolidat)

PI: Xavier Gasull
Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR)
2014_SGR_1165
01/01/2014-31/12/2016

  • RETIC Oftared: Prevención, detección precoz, tratamiento y rehabilitación de las patologías oculares

PI: Xavier Gasull
Instituto de Salud Carlos III
RD16/0008/0014
01/01/2017 - 31/12/2021

For more information for PI publications click in the link:
ORCID: https://orcid.org/0000-0002-6154-8323
ResearcherID: http://www.researcherid.com/rid/T-9630-2017
Loop profile: https://loop.frontiersin.org/people/21648/overview

Castellanos A, Pujol-Coma A, Andres-Bilbe A, Negm A, Callejo G, Soto D, Noël J, Comes N, Gasull X. TRESK background K+ channel deletion selectively uncovers enhanced mechanical and cold sensitivity. J Physiol. 2020 Mar; 598(5): 1017-1038. doi: 10.1113/ JP279203. PMID: 31919847

Jérôme Busserolles J, Gasull X, Noël J. Potassium Channels and Pain. In: The Oxford Handbook of the Neurobiology of Pain. Edited by John N. Wood. Oxford University Press. Dec 2019 DOI: 10.1093/ oxfordhb/ 9780190860509.013. 19. ISBN: 9780190860509

Soto D, Olivella M, Grau C, Armstrong J, Alcon C, Gasull X, Santos-Gómez A, Locubiche S, Gómez de Salazar M, García-Díaz R, Gratacòs-Batlle E, Ramos-Vicente D, Chu-Van E, Colsch B, Fernández-Dueñas V, Ciruela F, Bayés À, Sindreu C, López-Sala A, García-Cazorla À, Altafaj X. l-Serine dietary supplementation is associated with clinical improvement of loss-of-function GRIN2B-related pediatric encephalopathy.  Sci Signal. 2019 Jun 18;12 (586). pii: eaaw0936. doi: 10.1126/ scisignal.aaw0936. PMID: 31213567

Coombs ID, Soto D, McGee TP, Gold MG, Farrant M, Cull-Candy SG. Homomeric GluA2(R) AMPA receptors can conduct when desensitized. Nat Commun. 2019 Sep 20;10(1): 4312. doi: 10.1038/ s41467-019-12280-9. PMID: 31541113

Ramos-Vicente D, Ji J, Gratacòs-Batlle E, Gou G, Reig-Viader R, Luís J, Burguera D, Navas-Perez E, García-Fernández J, Fuentes-Prior P, Escriva H, Roher N, Soto D, Bayés À. Metazoan evolution of glutamate receptors reveals unreported phylogenetic groups and divergent lineage-specific events. Elife. 2018; 7: e35774. doi: 10.7554/ eLife.35774. PMID: 30465522

Pérez-Verdaguer M, Capera J, Ortego-Domínguez M, Bielanska J, Comes N, Montoro RJ, Camps M, Felipe A.Caveolar targeting links Kv1.3 with the insulin-dependent adipocyte physiology. Cell Mol Life Sci. 2018 Nov;75(21): 4059-4075. doi: 10.1007/ s00018-018-2851-7. Epub 2018 Jun 11. PMID: 29947924

Gasull X, Castany M, Castellanos A, Rezola M, Andrés-Bilbé A, Canut MI, Estévez R, Borrás T, Comes N. The LRRC8-mediated volume-regulated anion channel is altered in glaucoma. Sci Rep. 2019 Apr 1;9(1): 5392. doi: 10.1038/ s41598-019- 41524-3. PMID:

Royal P, Andres-Bilbe A, Ávalos Prado P, Verkest C, Wdziekonski B, Schaub S, Baron A, Lesage F, Gasull X, Levitz J, Sandoz G. Migraine-Associated TRESK Mutations Increase Neuronal Excitability through Alternative Translation Initiation and Inhibition of TREK. Neuron. 2019 Jan 16;101 (2): 232-245.e6. doi: 10.1016 /j.neuron. 2018.11.039. Epub 2018 Dec 17. PMID: 30573346

Petit-Pedrol M, Sell J, Planagumà J, Mannara F, Radosevic M, Haselmann H, Ceanga M, Sabater L, Spatola M, Soto D, Gasull X, Dalmau J, Geis C. LGI1 antibodies alter Kv1.1 and AMPA receptors changing synaptic excitability, plasticity and memory. Brain. 2018 Nov 1;141(11): 3144-3159. doi: 10.1093/ brain/ awy253. PMID: 30346486

Gratacòs-Batlle E, Olivella M, Sánchez-Fernández N, Yefimenko N, Miguez-Cabello F, Fadó R, Casals N, Gasull X, Ambrosio S, Soto D. Mechanisms of CPT1C-Dependent AMPAR Trafficking Enhancement. Front Mol Neurosci. 2018 Aug 8;11:275. doi: 10.3389/ fnmol.2018.00275. eCollection 2018. PMID: 30135643

Elorza-Vidal X, Sirisi S, Gaitán-Peñas H, Pérez-Rius C, Alonso-Gardón M, Armand-Ugón M, Lanciotti A, Brignone MS, Prat E, Nunes V, Ambrosini E, Gasull X, Estévez R. GlialCAM/MLC1 modulates LRRC8/VRAC currents in an indirect manner: Implications for megalencephalic leukoencephalopathy. Neurobiol Dis. 2018 Nov;119:88-99. 

Haselmann H, Mannara F, Werner C, Planagumà J, Miguez-Cabello F, Schmidl L, Grünewald B, Petit-Pedrol M, Kirmse K, Classen J, Demir F, Klöcker N, Soto D, Doose S, Dalmau J, Hallermann S, Geis C. Human Autoantibodies against the AMPA Receptor Subunit GluA2 Induce Receptor Reorganization and Memory Dysfunction. Neuron. 2018 Aug 18. pii: S0896-6273(18)30646-9. doi: 10.1016/j.neuron.2018.07.048. [Epub ahead of print]

Gratacòs-Batlle E, Olivella M, Sánchez-Fernández N, Yefimenko N, Miguez-Cabello F, Fadó R, Casals N, Gasull X, Ambrosio S, Soto D. Mechanisms of CPT1C-Dependent AMPAR Trafficking Enhancement. Front Mol Neurosci. 2018 Aug 8;11:275

Giblin JP, Etayo I, Castellanos A, Andres-Bilbe A, Gasull X. Anionic Phospholipids Bind to and Modulate the Activity of Human TRESK Background K+ Channel. Mol Neurobiol. 2018 Jul 23. doi: 10.1007/s12035-018-1244-0. [Epub ahead of print]

Leiva R, Phillips MB, Turcu AL, Gratacòs-Batlle E, León-García L, Sureda FX, Soto D, Johnson JW, Vázquez S. Pharmacological and Electrophysiological Characterization of Novel NMDA Receptor Antagonists. ACS Chem Neurosci. 2018 Jun 1. doi: 10.1021/acschemneuro.8b00154. [Epub ahead of print]

Castellanos A, Andres A, Bernal L, Callejo G, Comes N, Gual A, Giblin JP, Roza C, Gasull X. Pyrethroids inhibit K2P channels and activate sensory neurons: basis of insecticide-induced paraesthesias. Pain. 2018 Jan;159(1):92-105

Gaitán-Peñas H, Apaja PM, Arnedo T, Castellanos A, Elorza-Vidal X, Soto D, Gasull X, Lukacs GL, Estévez R. Leukoencephalopathy-causing CLCN2 mutations are associated with impaired Cl- channel function and trafficking. J Physiol. 2017 Nov 15;595(22):6993-7008

Carreon TA, Castellanos A, Gasull X, Bhattacharya SK. Interaction of cochlin and mechanosensitive channel TREK-1 in trabecular meshwork cells influences the regulation of intraocular pressure. Sci Rep. 2017 Mar 28; 7(1):452.

Sirisi S, Elorza-Vidal X, Arnedo T, Armand-Ugón M, Callejo G, Capdevila-Nortes X, López-Hernández T, Schulte U, Barrallo-Gimeno A, Nunes V, Gasull X*, Estévez R*. Depolarization causes the formation of a ternary complex between GlialCAM, MLC1 and ClC-2 in astrocytes: implications in megalencephalic leukoencephalopathy. Hum Mol Genet. 2017 Apr 7. [Epub ahead of print] *co-senior author

Martínez-Mármol R, Styrczewska K, Pérez-Verdaguer M, Vallejo-Gracia A, Comes N, Sorkin A, Felipe A. Ubiquitination mediates Kv1.3 endocytosis as a mechanism for protein kinase C-dependent modulation. Scientific Reports, 2017, 10(7): 42395.

Mirallave A, Morales M, Cabib C, Muñoz EJ, Santacruz P, Gasull X, Valls-Sole J. Sensory processing in Huntington's disease. Clin Neurophysiol. 2017 May; 128(5):689-696.

Kovács I, Luna C, Quirce S, Mizerska K, Callejo G, Riestra A, Fernández-Sánchez L, Meseguer VM, Cuenca N, Merayo-Lloves J, Acosta MC, Gasull X*, Belmonte C*, Gallar J*. Abnormal activity of corneal cold thermoreceptors underlies the unpleasant sensations in dry eye disease. Pain. 2016 Feb; 157(2):399-417. *co-senior author

Giblin JP, Comes N, Strauss O, Gasull X. Ion Channels in the Eye: Involvement in Ocular Pathologies. Adv Protein Chem Struct Biol. 2016: 104, pp.157-231.

López-Serrano C, Torres-Espín A, Hernández J, Alvarez-Palomo AB, Requena J, Gasull X, Edel MJ, Navarro X. Effects of the spinal cord injury environment on the differentiation capacity of human neural stem cells derived from induced pluripotent stem cells. Cell Transplant. 2016: 25, pp.1833-1852

Pérez-Verdaguer M, Capera J, Martínez-Mármol R, Camps M, Comes N, Tamkun MM, Felipe A. Caveolin interaction governs Kv1.3 lipid raft targeting. Scientific Reports, 2016, 2(6): 22453.

Martínez-Mármol R, Comes N, Pérez-Verdaguer M, Vicente R, Pujadas Ll, Soriano, E, Sorkin A, Felipe A. Unconventional EGF-induced ERK1/2-mediated Kv1.3 endocytosis. Cellular and Molecular Life Sciences 2016, 73(7): 1515-28.

Martínez-Mármol R, Barneda-Zahonero B, Soto D, Andrés RM, Coccia E, Gasull X, Planells-Ferrer L, Moubarak RS, Soriano E, Comella JX. FAIM-L regulation of XIAP degradation modulates Synaptic Long-Term Depression and Axon Degeneration. Sci Rep. 2016 Oct 21; 6:35775.

Figueiro-Silva J, Gruart A, Clayton KB, Podlesniy P, Abad MA, Gasull X, Delgado-García JM, Trullas R. Neuronal pentraxin 1 negatively regulates excitatory synapse density and synaptic plasticity. J Neurosci. 2015 Apr 8; 35 (14):5504-21.

Quintana P, Soto D, Poirot O, Zonouzi M, Kellenberger S, Muller D, Chrast R, Cull-Candy SG. (2015) Acid-sensing ion channel 1a drives AMPA receptor plasticity following ischaemia and acidosis in hippocampal CA1 neurons. J Physiol. 2015 Oct 1; 593(19):4373-86.

Espinosa-Parrilla JF, Martínez-Moreno M, Gasull X, Mahy N, Rodríguez MJ. The L-type voltage-gated calcium channel modulates microglial pro-inflammatory activity. Mol Cell Neurosci. 2015 Jan; 64:104-15.

Fadó R, Soto D, Miñano-Molina AJ, Pozo M, Carrasco P, Yefimenko N, Rodríguez-Álvarez J, Casals N (2015) Novel Regulation of the Synthesis of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptor Subunit GluA1 by Carnitine Palmitoyltransferase 1C (CPT1C) in the Hippocampus. J Biol Chem. 2015 Oct 16; 290(42):25548-60.

Moreno C, Oliveras A, de la Cruz A, Bartolucci Ch, Muñoz C, Salar E, Gimeno JR, Severi S, Comes N, Felipe A, Gonzalez T, Lambiase P, Valenzuela C. A new KCNQ1 mutation at the S5 segment that impairs its association with KCNE1 is responsible for short QT syndrome. Cardiovascular Research 2015, 107(4): 613-23.

Moreno C, de la Cruz A, Oliveras A, Kharche SR, Guizy M, Comes N, Starý T, Ronchi C, Rocchetti M, Baró I, Loussouarn G, Zaza A, Severi S, Felipe A, Valenzuela C. Marine n-3 PUFAs modulate IKs gating, channel expression, and location in membrane domains. Cardiovascular Research 2015, (2): 223-32.

Gratacòs-Batlle E, Yefimenko N, Cascos-García H, Soto D (2015) AMPAR interacting protein CPT1C enhances surface expression of GluA1-containing receptors. Front Cell Neurosci. 2015 Feb 2; 8:469.

Comes N, Felipe A. Involvement of potassium channels in the progression of cancer to a more malignant phenotype. Biochimica et Biophysica Acta-Biomembranes 2015 Oct; 1848(10 Pt B):2477-92.

Callejo G, Castellanos A, Castany M, Gual A, Luna C, Acosta MC, Gallar J, Giblin JP, Gasull X. Acid-sensing ion channels detect moderate acidifications to induce ocular pain. Pain. 2015 Mar; 156(3) :483-95.

Soto D, Coombs ID, Gratacòs-Batlle E, Farrant M, Cull-Candy SG. (2014) Molecular mechanisms contributing to TARP regulation of channel conductance and polyamine block of calcium-permeable AMPA receptors. J Neurosci. 34 (35):11673-83.

Oliveras A, Roura-Ferrer M, Solé L, de la Cruz A, Prieto A, Etxebarria A, Manils J, Morales-Cano D, Condom E, Soler C, Cogolludo A, Valenzuela C, Villarroel A, Comes N, Felipe A. Functional assembly of Kv7.1/Kv7.5 channels with emerging properties on vascular muscle physiology. Arteriosc Thromb and Vasc Biol, 2014 (7): 1522-30.

Guzman-Aranguez A, Gasull X, Diebold Y, Pintor J. Purinergic receptors in ocular inflammation. Mediators Inflamm. 2014; 2014:320906.

Capdevila-Nortes X, López-Hernández T, Apaja PM, López de Heredia M, Sirisi S, Callejo G, Arnedo T, Nunes V, Lukacs GL, Gasull X, Estévez R. Insights into MLC pathogenesis: GlialCAM is an MLC1 chaperone required for proper activation of volume-regulated anion currents. Hum Mol Genet. 2013 Nov 1; 22(21):4405-16.

Martínez-Mármol R, Pérez-Verdaguer M, Roig SR, Vallejo-Gracia A, Gotsi P, Serrano-Albarrás A, Bahamonde MI, Ferrer-Montiel A, Fernández-Ballester G, Comes N, Felipe A. A non-canonical di-acidic signal at the C-terminus of Kv1.3 determines anterograde trafficking and surface expression. Journal of Cell Science, 2013 (126): 5681-5691.

Comes N, Bielanska J, Vallejo-Gracia A, Serrano-Albarrás A, Marruecos L, Gómez D, Soler C, Condom E, Ramón Y Cajal S, Hernández-Losa J, Ferreres JC, Felipe A. The voltage-dependent K+ channels Kv1.3 and Kv1.5 in human cancer. Frontiers in Physiology, 2013 (4): 1-13.

Vallejo-Gracia A, Bielanska J, Hernández-Losa J, Castellví J, Ruiz-Marcellan MC, Ramón y Cajal S, Condom E, Manils J, Soler C, Comes N, Ferreres JC, Felipe A. Emerging role for the voltage-dependent K+ channel Kv1.5 in B-lymphocyte physiology: expression associated with human lymphoma malignancy. Journal of Leukocyte Biology, 2013 (94): 779-789.

Callejo G, Giblin JP, Gasull X. Modulation of TRESK background K+ channel by membrane stretch. PLoS One. 2013 May 15;8(5):e64471.

Delaunay A*, Gasull X*, Salinas M, Noël J, Friend V, Lingueglia E, Deval E. Human ASIC3 channel dynamically adapts its activity to sense the extracellular pH in both acidic and alkaline directions. Proc Natl Acad Sci U S A. 2012 Aug 7; 109(32):13124-9. *Co-authors

Coombs ID, Soto D, Zonouzi M, Renzi M, Shelley C, Farrant M, Cull-Candy SG (2012). Cornichons modify channel properties of recombinant and glial AMPA receptors. J Neurosci. 2012 Jul 18; 32(29) :9796-804.

Bats C, Soto D, Studniarczyk D, Farrant M, Cull-Candy SG. Channel properties reveal differential expression of TARPed and TARPless AMPARs in stargazer neurons. Nat Neurosci. 2012 Jun; 15(6):853-61.

N. Comes; A. Felipe. Regulation of K+ channels by cholesterol-rich membrane domains in immune system. Cholesterol Regulation of Ion Channels and Receptors. First Edition. Edited by Irena Levitan & Francisco J. Barrantes. Published 2012 by John Wiley & Sons, Inc. Book Chapter: 135-160.

Felipe, A.; Bielanska, J.; Comes, N.; Vallejo, A.; Roig, S.; Ramón y Cajal, S.; Condom, E.; Hernández-Losa, J.; Ferreres, J.C. Targeting the voltage-dependent K+ channels Kv1.3 and Kv1.5 as tumor biomarkers for cancer detection and prevention. Current Medicinal Chemistry, 2012 (19): 661-6

Roura-Ferrer, M.; Solé, L.; Oliveras, A.; Villarroel, A.; Comes, N.; Felipe, A. Targeting of Kv7.5 (KCNQ5)/KCNE channels to surface microdomains of cell membranes. Muscle and Nerve, 2012 (45): 48-54.

Colligris B, Crooke A, Gasull X, Escribano J, Herrero-Vanrell R, Benitez-del-Castillo JM, García-Feijoo J, Pintor J. Recent patents and developments in glaucoma biomarkers. Recent Pat Endocr Metab Immune Drug Discov. 2012 Sep; 6(3):224-34.

Jeworutzki E, López-Hernández T, Capdevila-Nortes X, Sirisi S, Bengtsson L, Montolio M, Zifarelli G, Arnedo T, Müller CS, Schulte U, Nunes V, Martínez A, Jentsch TJ, Gasull X, Pusch M, Estévez R. GlialCAM, a protein defective in a leukodystrophy, serves as a ClC-2 Cl(-) channel auxiliary subunit. Neuron. 2012 Mar 8; 73(5):951-61.

Deval E, Noël J, Gasull X, Delaunay A, Alloui A, Friend V, Eschalier A, Lazdunski M, Lingueglia E. Acid-sensing ion channels in postoperative pain. J Neurosci. 2011 Apr 20; 31(16):6059-66.

Jackson AC, Milstein AD, Soto D, Farrant M, Cull-Candy SG, Nicoll RA. Probing TARP modulation of AMPA receptor conductance with polyamine toxins. J Neurosci. 2011 May 18; 31(20):7511-20.

Comes N; Buie LK; Borrás T. Evidence for a role of angiopoietin-like 7 (ANGPTL7) in extracellular matrix formation of the human trabecular meshwork: implications for glaucoma. Genes to cells, 2011 (16): 243-259.

Castany M, Jordi I, Catala J, Gual A, Morales M, Gasull X, Pintor J. Glaucoma patients present increased levels of diadenosine tetraphosphate, Ap(4)A, in the aqueous humour. Exp Eye Res. 2011 Mar; 92(3):221-6.

Tulleuda A, Cokic B, Callejo G, Saiani B, Serra J, Gasull X. TRESK channel contribution to nociceptive sensory neurons excitability: modulation by nerve injury. Mol Pain. 2011 Apr 28; 7:30.

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