RT info:eu-repo/semantics/article
T1 Pharmacological Approaches for the Modulation of the Potassium Channel KV4.x and KChIPs
A1 Cercós, Pilar
A1 Peraza, Diego A.
A1 Benito-Bueno, Angela de
A1 Socuéllamos, Paula G.
A1 Aziz-Nignan, Abdoul
A1 Arrechaga-Estévez, Dariel
A1 Beato, Escarle
A1 Peña-Acevedo, Emilio
A1 Albert, Armando
A1 González-Vera, Juan A.
A1 Rodríguez, Yoel
A1 Martín-Martínez, Mercedes
A1 Valenzuela, Carmen
A1 Gutiérrez-Rodríguez, Marta
AB 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.
YR 2021
FD 2021
LK https://uvadoc.uva.es/handle/10324/66033
UL https://uvadoc.uva.es/handle/10324/66033
LA spa
NO Int J Mol Sci . 2021 Jan 31;22(3):1419. doi: 10.3390/ijms22031419.
DS UVaDOC
RD 18-nov-2024