Ion Signaling and Disease in Excitable Membranes

Group leader
Alvaro Villarroel

Biofisika Institute (CSIC-UPV/EHU)
Science Park of the UPV/EHU
Barrio Sarriena s/n. 48940 Leioa, Bizkaia (Spain)

Research goal

Among ionic channels, those that are potassium selective are, by far, the most diverse group. They play a key role in processes such as immune response, cell differentiation, excitability and cell death, among others. More than 60 genes for potassium channels are known in the human genome, which together with the fact that up to four different subunits can combine to form a channel, means that there are a large number of variants. Despite this impressive redundancy in “potassium permeation”, mutations in some subunits cause hereditary diseases, indicating that the rest of the channels cannot substitute for them. These diseases are known as channelopathies. To date, around 10 potassium channelopathies have been identified and four of these are due to mutations in genes of the KCNQ family, the gene products of which are Kv7.1-Kv7.5. Our research is focused on the molecular study of these proteins that regulate cell excitability.

Group members
PhD Student
Postdoctoral Fellow
CSIC Scientist

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Baltasar-Marchueta M, Llona L, M-Alicante S, Barbolla I, Ibarluzea MG, Ramis R, Salomon AM, Fundora B, Araujo A, Muguruza-Montero A, Nuñez E, Pérez-Olea S, Villanueva C, Leonardo A, Arrasate S, Sotomayor N, Villarroel A, Bergara A, Lete E, González-Díaz H

Identification of Riluzole derivatives as novel calmodulin inhibitors with neuroprotective activity by a joint synthesis, biosensor, and computational guided strategy
Biomed Pharmacother. 2024 May;174:116602
doi: 10.1016/j.biopha.2024.116602

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Saez-Matia A, Ibarluzea MG, M-Alicante S, Muguruza-Montero A, Nuñez E, Ramis R, Ballesteros OR, Lasa-Goicuria D, Fons C, Gallego M, Casis O, Leonardo A, Bergara A, Villarroel A.

MLe-KCNQ2: An Artificial Intelligence Model for the Prognosis of Missense KCNQ2 Gene Variants
Int J Mol Sci. 2024 Mar 2;25(5):2910
doi: 10.3390/ijms25052910

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Nuñez E, Jones F, Muguruza-Montero A, Urrutia J, Aguado A, Malo C, Bernardo-Seisdedos G, Domene C, Millet O, Gamper N, Villarroel A.

Redox regulation of K(V)7 channels through EF3 hand of calmodulin
Elife. 2023 Feb 20;12:e81961
DOI: 10.7554/eLife.81961

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Ramis R, Ballesteros ÓR, Muguruza-Montero A, M-Alicante S, Núñez E, Villarroel Á, Leonardo A, Bergara A.

Molecular dynamics simulations of the calmodulin-induced α-helix in the SK2 calcium-gated potassium ion channel
J Biol Chem. 2023 Feb;299(2):102850
DOI: 10.1016/j.jbc.2022.102850

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Revuelta M, Urrutia J, Villarroel A, Casis O.

Microglia-Mediated Inflammation and Neural Stem Cell Differentiation in Alzheimer's Disease: Possible Therapeutic Role of K(V)1.3 Channel Blockade
Front Cell Neurosci. 2022 Apr 21;16:868842
DOI: 10.3389/fncel.2022.868842

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Muguruza-Montero A, Ramis R, Nuñez E, R Ballesteros O, G Ibarluzea M, Araujo A, M-Alicante S, Urrutia J, Leonardo A, Bergara A, Villarroel A.

Do calmodulin binding IQ motifs have built-in capping domains?
Protein Sci. 2021 Oct;30(10):2029-2041
DOI: 10.1002/pro.4170

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Urrutia J, Aguado A, Gomis-Perez C, Muguruza-Montero A, Ballesteros OR, Zhang J, Nuñez E, Malo C, Chung HJ, Leonardo A, Bergara A, Villarroel A.

An epilepsy-causing mutation leads to co-translational misfolding of the Kv7.2 channel
BMC Biol. 2021 May 21;19(1):109
DOI: 10.1186/s12915-021-01040-1