The Role of Kv7 Channels in Neural Plasticity and Behavior.

Brian C Baculis,Hee Jung Chung,Jiaren Zhang

doi:10.3389/fphys.2020.568667

Brian C Baculis, Hee Jung Chung + Show 1 more

Open Access

https://doi.org/10.3389/fphys.2020.568667

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Abstract

Activity-dependent persistent changes in neuronal intrinsic excitability and synaptic strength are widely thought to underlie learning and memory. Voltage-gated KCNQ/Kv7 potassium channels have been of great interest as the potential targets for memory disorders due to the beneficial effects of their antagonists in cognition. Importantly, de novo dominant mutations in their neuronal subunits KCNQ2/Kv7.2 and KCNQ3/Kv7.3 are associated with epilepsy and neurodevelopmental disorder characterized by developmental delay and intellectual disability. The role of Kv7 channels in neuronal excitability and epilepsy has been extensively studied. However, their functional significance in neural plasticity, learning, and memory remains largely unknown. Here, we review recent studies that support the emerging roles of Kv7 channels in intrinsic and synaptic plasticity, and their contributions to cognition and behavior.

Highlights

Voltage-gate channel potassium (K+) subfamily Q member 1–5 (KCNQ 1–5) encodes Kv7.1–Kv7.5 channels (Gutman et al, 2005) that are critical regulators of excitability in neurons, muscles, and sensory cells (Soldovieri et al, 2011)
Kv7 Channels in Neural Plasticity burst firing of action potentials (APs; Brown and Passmore, 2009). Their functional significance in inhibiting neuronal excitability is underscored by the fact that mutations in their subunits cause epilepsy (Nappi et al, 2020), whereas Kv7 agonist retigabine inhibits seizures in rodents and humans (Miceli et al, 2008)
Conditional deletion of KCNQ2 and KCNQ3 increases the frequency of spontaneous excitatory postsynaptic currents (EPSC) in CA1 neurons (Soh et al, 2018), suggesting enhanced presynaptic release at CA1–CA3 synapses

Summary

INTRODUCTION

Voltage-gate channel potassium (K+) subfamily Q member 1–5 (KCNQ 1–5) encodes Kv7.1–Kv7.5 channels (Gutman et al, 2005) that are critical regulators of excitability in neurons, muscles, and sensory cells (Soldovieri et al, 2011). Kv7 Channels in Neural Plasticity burst firing of action potentials (APs; Brown and Passmore, 2009) Their functional significance in inhibiting neuronal excitability is underscored by the fact that mutations in their subunits cause epilepsy (Nappi et al, 2020), whereas Kv7 agonist retigabine inhibits seizures in rodents and humans (Miceli et al, 2008). EE patients display severe and often drug-resistant neonatal seizures and psychomotor retardation (Weckhuysen et al, 2012), and de novo EE mutations in KCNQ2 and KCNQ3 induce multiple defects in current and surface expression of Kv7 channels (Weckhuysen et al, 2012, 2013; Milh et al, 2013; Miceli et al, 2015; Kim et al, 2018; Zhang et al, 2020).

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