KCNQs: Ligand- and Voltage-Gated Potassium Channels.

Geoffrey W Abbott

doi:10.3389/fphys.2020.00583

Abstract

Voltage-gated potassium (Kv) channels in the KCNQ (Kv7) family are essential features of a broad range of excitable and non-excitable cell types and are found in organisms ranging from Hydra vulgaris to Homo sapiens. Although they are firmly in the superfamily of S4 domain-bearing voltage-sensing ion channels, KCNQ channels are highly sensitive to a range of endogenous and exogenous small molecules that act directly on the pore, the voltage-sensing domain, or the interface between the two. The focus of this review is regulation of KCNQs by direct binding of neurotransmitters and metabolites from both animals and plants and the role of the latter in the effects of plants consumed for food and as traditional folk medicines. The conceptual question arises: Are KCNQs voltage-gated channels that are also sensitive to ligands or ligand-gated channels that are also sensitive to voltage?

Highlights

Ion channels provide aqueous conduits across cell membranes that allow transmembrane movement of aqueous ions down their electrochemical gradient and across the hydrophobic interior of the lipid bilayer
We subsequently identified additional KCNE3 residues at the membrane-proximal region of the extracellular portion of KCNE3 (D54, D55), which interact with KCNQ1–S4 as part of the constitutive activation process (Choi and Abbott, 2010)
GABOB is a partial agonist of GABAB receptors and a GABAA receptor agonist, and we recently found that GABOB is a high-potency partial agonist of KCNQ2/3 channels

Summary

Introduction

Ion channels provide aqueous conduits across cell membranes that allow transmembrane movement of aqueous ions down their electrochemical gradient and across the hydrophobic interior of the lipid bilayer. Results from voltage-clamp fluorometry experiments suggest that retigabine binding to the KCNQ3 pore module stabilizes both the open state of the pore module and the activated step of the VSD, resulting in greatly slowed channel closing or deactivation under basal PIP2 conditions (Kim et al, 2017).

Results

Conclusion