Polyclonal Rabbit KCNQ4 Antibody
- Known as:
- Polyclonal Rabbit KCNQ4 Antibody
- Catalog number:
- KA1891
- Product Quantity:
- 100ul
- Category:
- -
- Supplier:
- KareBay
- Gene target:
- Polyclonal Rabbit KCNQ4 Antibody
Related genes to: Polyclonal Rabbit KCNQ4 Antibody
- Gene:
- KCNQ4 NIH gene
- Name:
- potassium voltage-gated channel subfamily Q member 4
- Previous symbol:
- DFNA2
- Synonyms:
- Kv7.4
- Chromosome:
- 1p34.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-02-05
- Date modifiied:
- 2019-04-23
Related products to: Polyclonal Rabbit KCNQ4 Antibody
Related articles to: Polyclonal Rabbit KCNQ4 Antibody
- Hypertension has been associated with altered nociceptive thresholds in humans and animal models, but the relationship between blood pressure (BP) and pain sensitivity remains inconsistent. Here, we investigated trigeminal nociception in male spontaneously hypertensive rats (SHRs) compared with normotensive Wistar-Kyoto (WKY) rats using operant facial pain assays, trigeminal ganglion (TG) electrophysiology, and bulk RNA sequencing with cell-type deconvolution. SHRs exhibited reduced thermal and mechanical facial pain sensitivity relative to WKY controls; however, measured systolic BP did not robustly explain the strain difference in thermal pain behavior. Whole-cell recordings of TG neurons revealed increased hyperpolarization-activated cyclic nucleotide-gated (HCN)-mediated currents and voltage-gated potassium currents in SHRs, while voltage-gated sodium currents were unchanged despite reduced expression of Scn8a, Scn9a, and Scn10a. Transcriptomic analysis further demonstrated broad downregulation of ion channel and sensory transduction genes in SHRs, including Hcn1, Hcn4, Kcnq3, Kcnq4, Piezo2, and Trpm8. Cell-type deconvolution revealed strain-dependent shifts in TG composition, including alterations in sensory neurons and non-neuronal populations such as immune cells, satellite glia, endothelial cells, pericytes, and Schwann cells. Together, these findings show that reduced trigeminal nociception in SHRs is associated with changes in TG ion channel function, sensory gene programs, and cell-type composition, while not being robustly explained by measured systolic BP. PERSPECTIVE: This study shows that reduced trigeminal pain in SHRs is associated with changes in ion channel function, gene expression, and TG cell-type composition, while not being robustly explained by measured systolic BP. - Source: PubMed
Publication date: 2026/06/20
Donertas-Ayaz BasakMurphy Niall PVivanco-Estela Airam NSapio Matthew RDe Paula Bruna BalbinoGuo SenMalphurs WendiSong QianqianNeubert John KCaudle Robert M - Hereditary hearing loss, the most prevalent genetic sensory disorder, lacks approved pharmacological therapies and represents a compelling target for gene correction. Pathogenic variants in KCNQ4 account for ~9.5% of autosomal dominant nonsyndromic cases. Prior gene-editing strategies disrupting mutant alleles have failed to achieve durable auditory rescue. Here we employed a knock-in mouse model harboring the human KCNQ4 c.961 G > A (p.G321S) mutation to evaluate precise base editing. Dual-AAV delivery of the adenine base editor ABE8e achieved 21.4-28.9% correction in the organ of Corti-the highest efficiency reported for genetic hearing loss. A dose-dependent therapeutic window emerged: higher doses promoted rapid recovery, whereas optimized lower doses minimized long-term toxicity and sustained functional benefit for at least 32 weeks. Treatment reduced auditory brainstem response thresholds by up to 49.09 dB SPL at optimal frequencies, mitigated degeneration of hair cells, spiral ganglion neurons, and auditory nerve fibers, and partially restored outer hair cell electrophysiology. These findings demonstrate the durability of precise mutation correction over allele-disruptive approaches and support clinical translation for KCNQ4-associated hearing loss. - Source: PubMed
Publication date: 2026/05/20
Kong YuxuanZhang YingjieXie ErjieLi XiaoPeng ZhuoxiZhang JingyuanZhao YuYuan Huijun - The medial olivocochlear (MOC) efferent system modulates outer hair cell (OHC) excitability and protects cochlea from overstimulation. Cholinergic activation of α9α10 nicotinic acetylcholine receptors (nAChRs) triggers Ca⁺ influx, activating BK and SK2 Ca⁺-dependent K⁺ channels, and K⁺ extrusion through KCNQ4 to restore membrane potential. KCNQ4-loss causes chronic depolarization, OHC dysfunction, and hearing loss. Here, we investigated how KCNQ4 deficiency affects cochlear efferent synapse development and organization. Using confocal immunofluorescence, we analyzed efferent innervation in the organ of Corti of Kcnq4 (KO) and Kcnq4 (WT) mice at 2, 3, 4, and 10 postnatal weeks (W). At 2 W, efferent terminals were similarly distributed between basal and lateral OHC membrane domains in both genotypes. During maturation, WT mice exhibited complete relocation of MOC terminals to the basal domain, whereas KO mice showed delayed maturation, with some terminals laterally displaced up to 10 W. KCNQ4 absence was associated with reduced number and volume of synaptic vesicles per efferent boutons on OHCs. Milder morphometric alterations were observed in efferent boutons within the inner hair cell region. At the molecular level, qPCR revealed downregulation of α10 nAChR subunit, BK, and SK2 transcripts in KO at 4 W, with recovery to 10 W. Despite this recovery, BK protein showed reduced expression, mislocalization, and disorganized synaptic plaques in OHCs. KO also displayed age-dependent upregulation of the calcium-binding proteins calbindin and calretinin, suggesting compensatory responses to altered Ca homeostasis. Together, these findings demonstrate that KCNQ4 is essential for OHC repolarization, maturation and maintenance of cochlear efferent synapses. - Source: PubMed
Publication date: 2026/05/01
Rías EzequielOuwerkerk IngridSpitzmaul GuillermoDionisio Leonardo - Approximately 200 genes have been identified as causative in hereditary hearing loss. Genetic testing is increasingly important, not only for accurate diagnosis but also for predicting audiometric profiles, prognoses, and potential syndromic features. Hereditary hearing loss can be syndromic or nonsyndromic, with nonsyndromic forms further classified by inheritance: autosomal-dominant or autosomal-recessive. In autosomal-dominant cases, three pathological mechanisms-haploinsufficiency, dominant-negative effects, and gain of function-are often implicated. Moreover, specific genes correlate with distinct audiometric patterns: WFS1 variants typically cause low-frequency hearing loss, whereas KCNQ4 and POU4F3 variants are linked to high-frequency loss. To investigate the underlying mechanisms of these frequency-dependent patterns, gene expression across cochlear turns was compared in mice, but interpretations of the results were limited because of inherent structural differences between rodent and primate cochleae. Therefore, the common marmoset (Callithrix jacchus), which offers closer anatomical and functional similarity to human cochleae, was utilized herein as an improved model. Using RNA sequencing (RNA-seq) across cochlear turns of common marmosets, the present study aimed to uncover gene expression and alternative splicing patterns that may explain tonotopic manifestations in hereditary hearing loss, including those caused by WFS1 variants, the present study being one such using common marmoset cochlear RNA-seq data, and these findings are highly valuable for genetic diagnosis and the development of gene therapies. - Source: PubMed
Publication date: 2026/02/07
Yokota ShuYoshimura HidekaneNishio Shin-YaSasaki ErikaMukasa KeisukeUsami Shin-IchiTakumi Yutaka - KCNQ4-encoded K7.4 voltage-gated potassium channels are expressed in hair-cells of the inner ear. Loss-of-function variants in KCNQ4 cause non-syndromic progressive hearing loss (DFNA2). K7.4 pore opening requires voltage-dependent conformational changes (activation) of the voltage-sensor domains (VSDs); however, how fast charge displacement during VSD activation is coupled to slow channel opening is currently unclear. Here, we optically tracked K7.4 VSD activation with voltage-clamp fluorometry, leveraging two fluorophores and pulsed excitation, and found that VSD activation comprises several voltage-dependent transitions, some with kinetics and voltage-dependence matching those of channel opening and closing. The DFNA2-causing R216H mutation impairs VSD movement and channel opening by destabilizing the active VSD configuration, a result confirmed by molecular dynamics simulations. We propose that the K7.4 VSD activates in two steps: a fast movement representing a first transition to an intermediate activation state, followed by slower component(s) that fully activate the VSD and drive channel opening. - Source: PubMed
Publication date: 2026/02/05
Nappi MarioFrampton Damon J AKusay Ali SWang KaiqianYasarbas S SuhedaPozzi SerenaMiceli FrancescoLiin Sara ITaglialatela MaurizioPantazis Antonios