Ask about this productRelated genes to: KCNH5 antibody
- Gene:
- KCNH5 NIH gene
- Name:
- potassium voltage-gated channel subfamily H member 5
- Previous symbol:
- -
- Synonyms:
- Kv10.2, H-EAG2, eag2
- Chromosome:
- 14q23.2
- Locus Type:
- gene with protein product
- Date approved:
- 2000-02-02
- Date modifiied:
- 2016-10-05
Related products to: KCNH5 antibody
Related articles to: KCNH5 antibody
- Voltage-gated K (Kv) channels are tetrameric complexes of proteins encoded by KCN genes. Gain-of-function (GoF) mutations in KCNH1 (Kv10.1, hEAG1) and KCNH5 (Kv10.2, hEAG2) give rise to developmental disorders, intellectual disability, and epilepsy. Currently, clinical symptoms are not straightforwardly associated with functional properties of mutated channels. Here we investigated how members of the KCNH subfamily are affected by heteromerization with mutant Kv10.1 or Kv10.2 protein subunits. The de novo variant Kv10.1-G496E, which leads to impaired neurodevelopment and epilepsy, was expressed alone or with other wild-type subunits in HEK293T cells and characterized using whole-cell patch clamp. While Kv10.1-G496E alone did not yield functional K channels, coexpression with Kv10.1 or Kv10.2 shifted the half-maximum voltage of activation in the hyperpolarizing direction. Likewise, the homologous mutation Kv10.2-G465E did not yield functional channels but also induced GoF upon coexpression with wild-type Kv10.1 or Kv10.2. By contrast, the mutants did not affect the function of Kv11.1 (KCNH2, hERG1) channels. To infer the relevance of Kv10 GoF mutations under physiological conditions, we used the fluorescent genetically encoded voltage indicator mK2-rEstus and found that both, Kv10.1 and Kv10.2, hyperpolarized HEK293T cells, and that coexpression of the GoF mutants augmented this hyperpolarization. Our findings imply that interpretation of clinical symptoms related to Kv10 GoF mutations requires considering the functional crosstalk with Kv10.1 and Kv10.2 subunits, which are both expressed in glutamatergic neurons in cortical Layers III and IV. - Source: PubMed
Publication date: 2026/02/08
Bernert AlisaRühl PhilippSchönherr RolandHeinemann Stefan H - Fentanyl is widely used perioperatively and illicitly as a drug of abuse. As a potent μ-opioid receptor agonist, fentanyl canonically inhibits excitability through Gα intracellular signalling pathways resulting in analgesia and respiratory depression. However, fentanyl also paradoxically activates respiratory muscles causing a potentially lethal effect termed wooden chest syndrome. Here we show that fentanyl, but not morphine, causes a persistent tonic component of diaphragmatic muscle activity. Voltage-clamp studies reveal that fentanyl directly blocks a subset of ether-à-go-go-class potassium (K) channels. These channels are widely expressed in spinal motoneurons, including those innervating the diaphragm. A significant fraction of these motoneurons are excited by fentanyl, concomitant with blockade of K currents. Taken together we identified a novel off-target mechanism for fentanyl action, independent of μ-opioid receptor activation. Our findings may inform the design of safer analgesics and generalize beyond the activation of motoneurons to other neuronal circuits implicated in fentanyl-related maladaptive behaviours. KEY POINTS: High doses of fentanyl can cause a lethal phenotype termed 'wooden chest syndrome' (WCS) resulting from tonic contractions of respiratory-associated musculature, precluding the ability to mechanically inflate the lungs. In vivo murine diaphragmatic electromyograms reveal a tonic component of muscle activity elicited by fentanyl, but not morphine. Fentanyl reversibly blocks a subset of ether-à-go-go (EAG)-class potassium channels (EAG/Kv10 and ERG/Kv11 subclasses) expressed in HEK293 cells. Computational docking of fentanyl into cryogenic electron microscopy structures of these potassium channels predicts a binding site beneath the K selectivity filter. RT-PCR and RNA-scope in situ experiments reveal widespread expression of EAG/Kv10 (Kcnh1, Kcnh5) and ERG/Kv11 (Kcnh2, Kcnh6, Kcnh7) transcripts in cervical motoneurons, including phrenic motoneurons retrogradely labelled from the diaphragm. In vitro patch-clamp recordings from cervical spinal sections identifies a significant fraction of phrenic motoneurons (44%) electrically excited by fentanyl, concomitant with the blockade of a non-inactivating voltage-gated potassium current. Direct block of EAG potassium channels by fentanyl may contribute to WCS. - Source: PubMed
Publication date: 2025/10/19
Wei Aguan DBurgraff Nicholas JOliveira Luiz MMoreira Thiago SRamirez Jan-Marino - C-X-C motif chemokine receptor 2 (CXCR2) plays a crucial role in inflammation and immunity, and the involvement of chemokine receptors in the tumor microenvironment is extensively documented. However, the impact of CXCR2 deficiency on the complete transcriptome, including mRNA and ncRNAs, in tumor cells remains unclear. - Source: PubMed
Dong WeiGao JifangMu YilinWang YanyanZhu XiaoyanWang JiayinZi Chen - Recent advances in exome and targeted sequencing have significantly improved the aetiological diagnosis of epilepsy, revealing an increasing number of epilepsy-related pathogenic genes. As a result, the diagnosis and treatment of epilepsy have become more accessible and more traceable. Voltage-gated potassium channels (Kv) regulate electrical excitability in neuron systems. Mutate Kv channels have been implicated in epilepsy as demonstrated in case reports and researches using gene-knockout mouse models. Both gain and loss-of-function of Kv channels lead to epilepsy with similar phenotypes through different mechanisms, bringing new challenges to the diagnosis and treatment of epilepsy. Research on genetic epilepsy is progressing rapidly, with several drug candidates targeting mutated genes or channels emerging. This article provides a brief overview of the symptoms and pathogenesis of epilepsy associated with voltage-gated potassium ion channels dysfunction and highlights recent progress in treatments. Here, we reviewed case reports of gene mutations related to epilepsy in recent years and summarized the proportion of Kv genes. Our focus is on the progress in precise treatments for specific voltage-gated potassium channel genes linked to epilepsy, including KCNA1, KCNA2, KCNB1, KCNC1, KCND2, KCNQ2, KCNQ3, KCNH1, and KCNH5. - Source: PubMed
Publication date: 2024/10/07
Zheng YitingChen Jing - We herein report a novel de novo KCNH5 variant in a patient with refractory epileptic encephalopathy. The patient exhibited seizures at 1 year and 7 months old, which gradually worsened, leading to a bedridden status. Brain magnetic resonance imaging (MRI) showed cerebral atrophy and cerebellar hypoplasia. A trio whole-exome sequence analysis identified a de novo heterozygous c.640A>C, p.Lys214Gln variant in KCNH5 that was predicted to be deleterious. Recent studies have linked KCNH5 to various epileptic encephalopathies, with many patients showing normal MRI findings. The present case expands the clinical spectrum of the disease, as it is characterized by severe neurological prognosis, cerebral atrophy, and cerebellar hypoplasia. - Source: PubMed
Publication date: 2024/08/01
Mitsutake AkihikoMatsukawa TakashiNaito TatsuhikoIshiura HiroyukiMitsui JunHarada HiroakiFujio KeishiFujishiro JunMori HarushiMorishita ShinichiTsuji ShojiToda Tatsushi