Pharmacological approaches for the modulation of the potassium channel KV4.x and KChIPs
AuthorCercós, Pilar; Peraza, Diego A.; Benito-Bueno, Angela de; 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
PublisherMDPI, Basel, Switzerland
10.3390/ijms22031419International Journal of Molecular Sciences 22.3 (2020): 1419
Funded byThis research was funded by Ministerio de Ciencia e Innovación (MICIU) Spain SAF2016- 75021-R and PID2019-104366RB-C21 (to CV), RTI2018-097189-B-C22 (to MMM), PID2019-104366RBC22 (to MG-R); the Instituto de Salud Carlos III CIBERCV program CB/11/00222 (to CV); and the Consejo Superior de Investigaciones Científicas grants: PIE 201820E104, 2019AEP148 (to CV), and 201880E109 (to MMM and MG-R). The cost of this publication was paid in part by funds from the European Fund for Economic and Regional Development (FEDER). PC held a postgraduate FPI fellowship from the Spanish Ministry of Economy, Industry, and Competitivity (MINECO). DAP held CSIC contracts. AdB-B holds a MICIU predoctoral contract (BES-2017-080184). PGS holds a MICIU predoctoral contract FPU2017/02731. AAN, DAE, EB, and EPA were sponsored by CUNY Research Scholars Program (CRSP) and Collegiate Science Technology Entry Program (CSTEP). YR is grateful to the Hostos Office of Academic Affairs for providing travel awards and the OpenEye Scientific Software for providing free academic licenses
ProjectGobierno de España. SAF2016-75021-R; Gobierno de España. PID2019-104366RB-C21; Gobierno de España.CB/11/00222; Gobierno de España. PIE 201820E104; Gobierno de España. PIE2019AEP148
SubjectsA-type current; K 4/KChIPs modulators V; Potassium channel interacting proteins (KChIPs); Protein–protein interactions; Transient outward current; Voltage-gated potassium channels K 4 V; Medicina
Rights© 2021 The authors
Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.
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 under-lying mechanism involving KV4-mediated-channelopathies, establishing the foundations for drug discovery, and hence their treatments.
Google Scholar:Cercós, Pilar - Peraza, Diego A. - Benito-Bueno, Angela de - 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
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