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Potassium voltage-gated channel subfamily KQT member 5 (KCNQ5) (Kv7.5)

Target
Kv7.5
Molecular classification
Ion channel, Voltage-gated potassium channel, KCNQ family
01

Overview

Potassium voltage-gated channel subfamily KQT member 5 (Kv7.5) is a transmembrane protein encoded by the KCNQ5 gene that forms voltage-gated potassium channels, primarily in the brain and smooth muscle [1, 2]. It is a key component of the M-current, which regulates neuronal excitability by controlling the resting membrane potential and preventing repetitive firing [1, 3]. In the central nervous system, Kv7.5 is localized in areas such as the hippocampus and cortex, where it influences synaptic plasticity and cognitive functions [3]. Pathogenic variants in KCNQ5 are linked to intellectual disability and epileptic encephalopathy, highlighting its critical role in neurodevelopment [3]. Additionally, Kv7.5 is expressed in vascular smooth muscle cells, where it contributes to the regulation of vascular tone and blood pressure [4]. Therapeutic strategies often involve positive allosteric modulators, such as retigabine, which enhance channel activity to treat conditions characterized by neuronal hyperexcitability [5]. However, developing selective ligands is difficult due to the high structural similarity between Kv7.5 and other members of the Kv7 family [5]. Sources: [1] UniProt (Q9NR82) [2] NCBI Gene (ID: 56479) [3] Lehman et al. (2017), PMID: 28942963 [4] Brueggemann et al. (2011), PMID: 21139043 [5] Gunthorpe et al. (2012), PMID: 22305715

Other names
KCNQ5Potassium channel protein KQT5Voltage-gated potassium channel subunit Kv7.5KQT-like 5
02

Mechanism of action

Positive allosteric modulation (channel opening) to stabilize the resting membrane potential and reduce neuronal firing; or channel inhibition to increase excitability in specific experimental contexts [1, 5].

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Biological functions

Regulation of neuronal excitabilityM-current generationMaintenance of resting membrane potentialRegulation of vascular toneSynaptic integration
04

Disease associations

EpilepsyIntellectual disabilityNeuropathic painHypertensionDevelopmental and epileptic encephalopathy
05

Safety considerations

CNS depression (dizziness, somnolence)Urinary retentionPotential for blue skin or retinal pigmentation (associated with retigabine)Off-target cardiac effects if Kv7.1 is cross-activated
06

Interacting drugs

Retigabine (Ezogabine)

5 more in the full profile.

07

Biomarkers

KCNQ5 genetic variantsElectroencephalogram (EEG) spike-wave discharges

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