Evaluation of Small-Molecule Candidates as Modulators of M-Type K+ Currents: Impacts on Current Amplitude, Gating, and Voltage-Dependent Hysteresis DOI Open Access

Te‐Ling Lu,

Rasa Liutkevičienė, Vita Rovīte

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1504 - 1504

Published: Feb. 11, 2025

The core subunits of the KV7.2, KV7.3, and KV7.5 channels, encoded by KCNQ2, KCNQ3, KCNQ5 genes, are expressed across various cell types play a key role in generating M-type K+ current (IK(M)). This is characterized an activation threshold at low voltages displays slow deactivation kinetics. Variations amplitude gating kinetics IK(M) can significantly influence membrane excitability. Notably, demonstrates distinct voltage-dependent hysteresis when subjected to prolonged isosceles-triangular ramp pulses. In this review, we explore small-molecule modulators that either inhibit or enhance IK(M), along with their perturbations on its hysteresis. inhibitors highlighted here include bisoprolol, brivaracetam, cannabidiol, nalbuphine, phenobarbital, remdesivir. Conversely, compounds such as flupirtine, kynurenic acid, naringenin, QO-58, solifenacin have been shown IK(M). These show potential pharmacological therapeutic strategies for treating certain disorders linked gain-of-function loss-of-function mutations (KV7x KCNQx) channels.

Language: Английский

Evaluation of Small-Molecule Candidates as Modulators of M-Type K+ Currents: Impacts on Current Amplitude, Gating, and Voltage-Dependent Hysteresis DOI Open Access

Te‐Ling Lu,

Rasa Liutkevičienė, Vita Rovīte

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1504 - 1504

Published: Feb. 11, 2025

The core subunits of the KV7.2, KV7.3, and KV7.5 channels, encoded by KCNQ2, KCNQ3, KCNQ5 genes, are expressed across various cell types play a key role in generating M-type K+ current (IK(M)). This is characterized an activation threshold at low voltages displays slow deactivation kinetics. Variations amplitude gating kinetics IK(M) can significantly influence membrane excitability. Notably, demonstrates distinct voltage-dependent hysteresis when subjected to prolonged isosceles-triangular ramp pulses. In this review, we explore small-molecule modulators that either inhibit or enhance IK(M), along with their perturbations on its hysteresis. inhibitors highlighted here include bisoprolol, brivaracetam, cannabidiol, nalbuphine, phenobarbital, remdesivir. Conversely, compounds such as flupirtine, kynurenic acid, naringenin, QO-58, solifenacin have been shown IK(M). These show potential pharmacological therapeutic strategies for treating certain disorders linked gain-of-function loss-of-function mutations (KV7x KCNQx) channels.

Language: Английский

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