Ask about this productRelated genes to: KCNH2 Blocking Peptide
- Gene:
- KCNH2 NIH gene
- Name:
- potassium voltage-gated channel subfamily H member 2
- Previous symbol:
- LQT2
- Synonyms:
- Kv11.1, HERG, erg1
- Chromosome:
- 7q36.1
- Locus Type:
- gene with protein product
- Date approved:
- 1993-03-22
- Date modifiied:
- 2019-04-23
Related products to: KCNH2 Blocking Peptide
Related articles to: KCNH2 Blocking Peptide
- Thyroid hormone (TH) is a critical regulator of skeletal muscle (SkM) physiology, influencing muscle development, metabolism and contractile function. However, the molecular mechanisms by which TH modulates muscle excitability and contraction remain incompletely defined. Here, we investigated the role of TH signalling in regulating SkM electrical activity through transcriptional control of ion channels. Using RNA sequencing of gastrocnemius muscles from wild-type (CTR), muscle-specific deiodinase type 2-deficient (mD2KO), and thyroid hormone receptor α/β-deficient (TRαKO/TRβKO) mice, we identified a shared transcriptional signature of TH deficiency characterized by the dysregulation of multiple ion channel genes. Notably, two potassium (K) channel-related genes Kcnh2 and Kcnk1, which encode for mERG1 and TWIK-1, respectively, were downregulated, while Kcnab1 was consistently upregulated in both mD2KO and TRαKO/TRβKO muscles compared with CTR, suggesting a common TH-dependent regulatory mechanism. To investigate whether such transcriptional remodelling of K channels translates into functional changes, we assessed the direct effects of TH on K currents using patch-clamp recordings in differentiated C2C12 cells exposed to TH as a model of physiological TH signalling. Interestingly, we found that TH treatment significantly increased mERG current density in differentiated C2C12 cells, supporting a role for TH signalling in the modulation of SkM electrical activity. Collectively, these results provide a mechanistic framework through which TH contributes to the regulation of muscle electrical stability, with potential implications for thyroid-related myopathies. KEY POINTS: Thyroid hormone (TH) regulates skeletal muscle excitability through transcriptional modulation of potassium (K) channel-related genes. RNA-seq analyses identified a TH-dependent signature with downregulation of Kcnh2 (mERG1) and Kcnk1 (TWIK-1), and upregulation of Kcnab1 under TH-deficient conditions. Chromatin immunoprecipitation demonstrates direct binding of TH receptors to regulatory regions of these channel genes. Electrophysiological recordings in differentiated C2C12 cells show that TH treatment increases mERG current density. This coordinated remodelling of K channel expression provides a mechanistic basis for TH-driven optimization of muscle electrical stability and contractile performance. These findings support a role for TH signalling in the regulation of skeletal muscle electrical stability, with potential implications for thyroid-related myopathies. - Source: PubMed
Publication date: 2026/06/18
Nappi AnnaritaMiro CaterinaCicatiello Annunziata GaetanaPiccialli IlariaSagliocchi SerenaAcampora LuciaRestolfer FedericaSirica RosaMurolo MelaniaCicco Emery DiTerracciano DanielaPannaccione AnnaDentice Monica - Takotsubo syndrome (TTS) is a condition first identified in the 1990s in the Japanese population. It is believed that 1%-2% of acute coronary syndromes are due to TTS. The pathophysiological mechanism involves acute activation of the sympathetic nervous system with a cataclysmic release of catecholamines, causing acute myocardial dysfunction. - Source: PubMed
Publication date: 2026/05/29
Georgiadis MiltiadisZiakos AthanasiosKamper LarsHaage PatrickSeyfarth MelchiorAbanador-Kamper Nadine - Ginkgo biloba extract (GBE) is commonly used to treat sudden sensorineural hearing loss (SSNHL), but its mechanisms are not fully understood. This study aimed to identify the bioactive components and therapeutic targets of GBE in SSNHL using network pharmacology and molecular docking. - Source: PubMed
Publication date: 2026/05/21
Huang QiaoRen YiZhu ZiangChen LongLiao XingweiYin Shihua - Corylin (3-(2,2-dimethylchromen-6-yl)-7-hydroxychromen-4-one), a bioactive flavonoid, has been reported to exercise anti-inflammatory, antineoplastic, and antioxidant effects, and may also possess lifespan-extending properties. Any modifications of transmembrane ionic currents produced by corylin remain largely unknown. The patch-clamp technique and docking prediction were used in this study. In pituitary GH somatolactotrophs, corylin concentration-dependently increased the magnitude of the M-type K current (), with an EC of 3.8 μM. Concurrently, the activation time constant of was shortened. The addition of linopirdine (10 μM), an inhibitor, suppressed the current amplitude. Corylin also induced a leftward shift in the steady-state activation curve and enhanced during pulse-train stimulation. Moreover, corylin increases the hysteretic strength of evoked by a long-lasting triangular ramp pulse; this effect was attenuated by linopirdine. The stimulatory effect of corylin on was not altered by carvedilol or iberiotoxin but was reduced by dapagliflozin. In contrast, depolarization-activated was not affected by 17β-estradiol alone. In cell-attached recordings, corylin increased M-type K (K)-channel activity with minimal change in single-channel amplitude, while prolonging the mean open time. This stimulatory effect was reversed by linopirdine or dapagliflozin. Additionally, corylin slightly inhibited the -mediated current. Docking analysis further suggested that corylin potentially interacts with residues in KCNQ2 or KCNH2 channels via hydrogen bonding and hydrophobic interactions. These findings suggest that corylin modulates ionic currents, primarily through K (KCNQ/K7) channels, which may underlie its in vivo actions and those of related flavonoids. These effects may contribute to the regulation of functional activities of neuronal, neuroendocrine, and endocrine cells. - Source: PubMed
Publication date: 2026/04/30
Wu Sheng-NanLiutkevičienė RasaLin Sheng-Che - Histone deacetylase (HDAC) inhibitors are approved for cancer treatment and are being investigated for a wide range of other diseases. Despite their therapeutic promise, clinical studies have reported cardiac side effects, particularly electrocardiogram (EKG) abnormalities, with QT interval prolongation being one of the most consistently reported findings. The mechanisms underlying these cardiac effects remain unclear. In this study, we investigated the role of HDAC3 in cardiac electrophysiology. We found that postnatal depletion of cardiac HDAC3 in mice caused QT interval prolongation, recapitulating the EKG abnormalities reported with HDAC inhibitor use. Adult-onset inducible depletion of cardiac HDAC3 induced additional EKG abnormalities, including T-wave flattening, inversion, and biphasic T waves, which are also observed clinically. Loss of HDAC3 deacetylase activity, without affecting HDAC3 protein levels, was sufficient to induce QT prolongation. Disruption of HDAC3 function altered the expression of ion channel genes, including the downregulation of potassium channel genes such as , , and . Moreover, a single dose of HDAC inhibitors, romidepsin or mocetinostat, caused reversible QT prolongation in mice. Consistent with these findings, HDAC inhibitor treatment altered the expression of potassium channel genes, with a predominant downregulation of multiple Kcn family members, including , , and . These findings establish HDAC3 enzymatic activity as a key regulator of cardiac repolarization and provide mechanistic insight into HDAC inhibitor-associated cardiotoxicity. - Source: PubMed
Publication date: 2026/05/14
Lu JiaoWard ChristopherQian SichongZhang LileiChang JiangSun Zheng