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Open AccessReview

Pharmacological Approaches for the Modulation of the Potassium Channel KV4.x and KChIPs

1
Instituto de Química Médica (IQM-CSIC), 28006 Madrid, Spain
2
Instituto de Investigaciones Biomédicas Alberto Sols (IIBM), CSIC-UAM, 28029 Madrid, Spain
3
Spanish Network for Biomedical Research in Cardiovascular Research (CIBERCV), Instituto de Salud Carlos III, 28029 Madrid, Spain
4
Department of Natural Sciences, Hostos Community College of CUNY, New York, NY 10451, USA
5
Instituto de Química Física Rocasolano (IQFR-CSIC), 28006 Madrid, Spain
6
Departamento de Físicoquímica, Facultad de Farmacia, Universidad de Granada, 18071 Granada, Spain
*
Authors to whom correspondence should be addressed.
Academic Editor: Antonio Ferrer-Montiel
Int. J. Mol. Sci. 2021, 22(3), 1419; https://doi.org/10.3390/ijms22031419
Received: 16 January 2021 / Revised: 27 January 2021 / Accepted: 28 January 2021 / Published: 31 January 2021
(This article belongs to the Special Issue Membrane Channels in Health and Diseases)
Ion channels are macromolecular complexes present in the plasma membrane and intracellular organelles of cells. Dysfunction of ion channels results in a group of disorders named channelopathies, which represent an extraordinary challenge for study and treatment. In this review, we will focus on voltage-gated potassium channels (KV), specifically on the KV4-family. The activation of these channels generates outward currents operating at subthreshold membrane potentials as recorded from myocardial cells (ITO, transient outward current) and from the somata of hippocampal neurons (ISA). In the heart, KV4 dysfunctions are related to Brugada syndrome, atrial fibrillation, hypertrophy, and heart failure. In hippocampus, KV4.x channelopathies are linked to schizophrenia, epilepsy, and Alzheimer’s disease. KV4.x channels need to assemble with other accessory subunits (β) to fully reproduce the ITO and ISA currents. β Subunits affect channel gating and/or the traffic to the plasma membrane, and their dysfunctions may influence channel pharmacology. Among KV4 regulatory subunits, this review aims to analyze the KV4/KChIPs interaction and the effect of small molecule KChIP ligands in the A-type currents generated by the modulation of the KV4/KChIP channel complex. Knowledge gained from structural and functional studies using activators or inhibitors of the potassium current mediated by KV4/KChIPs will better help understand the underlying mechanism involving KV4-mediated-channelopathies, establishing the foundations for drug discovery, and hence their treatments. View Full-Text
Keywords: voltage-gated potassium channels KV4; transient outward current; A-type current; potassium channel interacting proteins (KChIPs); protein–protein interactions; KV4/KChIPs modulators voltage-gated potassium channels KV4; transient outward current; A-type current; potassium channel interacting proteins (KChIPs); protein–protein interactions; KV4/KChIPs modulators
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MDPI and ACS Style

Cercós, P.; Peraza, D.A.; Benito-Bueno, A.d.; Socuéllamos, P.G.; Aziz-Nignan, A.; Arrechaga-Estévez, D.; Beato, E.; Peña-Acevedo, E.; Albert, A.; González-Vera, J.A.; Rodríguez, Y.; Martín-Martínez, M.; Valenzuela, C.; Gutiérrez-Rodríguez, M. Pharmacological Approaches for the Modulation of the Potassium Channel KV4.x and KChIPs. Int. J. Mol. Sci. 2021, 22, 1419. https://doi.org/10.3390/ijms22031419

AMA Style

Cercós P, Peraza DA, Benito-Bueno Ad, Socuéllamos PG, Aziz-Nignan A, Arrechaga-Estévez D, Beato E, Peña-Acevedo E, Albert A, González-Vera JA, Rodríguez Y, Martín-Martínez M, Valenzuela C, Gutiérrez-Rodríguez M. Pharmacological Approaches for the Modulation of the Potassium Channel KV4.x and KChIPs. International Journal of Molecular Sciences. 2021; 22(3):1419. https://doi.org/10.3390/ijms22031419

Chicago/Turabian Style

Cercós, Pilar; Peraza, Diego A.; Benito-Bueno, Angela d.; Socuéllamos, Paula G.; Aziz-Nignan, Abdoul; Arrechaga-Estévez, Dariel; Beato, Escarle; Peña-Acevedo, Emilio; Albert, Armando; González-Vera, Juan A.; Rodríguez, Yoel; Martín-Martínez, Mercedes; Valenzuela, Carmen; Gutiérrez-Rodríguez, Marta. 2021. "Pharmacological Approaches for the Modulation of the Potassium Channel KV4.x and KChIPs" Int. J. Mol. Sci. 22, no. 3: 1419. https://doi.org/10.3390/ijms22031419

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