Kv1.5 potassium channel inhib 
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  • ||||||||||  Frameshift Mutation in LMNA Gene Causes Atrial Arrhythmogenesis via Epigenetic Inhibition of KCNA5 Expression (Moderated Digital Posters 1, Science and Technology Hall, Level 2) -  Sep 21, 2023 - Abstract #AHA2023AHA_6518;    
    Our study validates the pathogenicity of LMNA frameshift mutation for the atrium and highlights epigenetic changes leading to KCNA5 expression downregulation and consequential phenotypic alterations. These results broaden the current knowledge of laminopathy beyond its previous emphasis on ventricular lesions, offering potential therapeutic targets for the disease.
  • ||||||||||  Journal, IO biomarker:  Cm28, a scorpion toxin having a unique primary structure, inhibits KV1.2 and KV1.3 with high affinity. (Pubmed Central) -  Jun 22, 2022   
    In a biological functional assay, Cm28 strongly inhibited the expression of the activation markers interleukin-2 receptor and CD40 ligand in anti-CD3-activated human CD4+ effector memory T lymphocytes. Cm28, due to its unique structure, may serve as a template for the generation of novel peptides targeting KV1.3 in autoimmune diseases.
  • ||||||||||  rosiglitazone / Generic mfg.
    Journal:  The antidiabetic drug rosiglitazone blocks Kv1.5 potassium channels in an open state. (Pubmed Central) -  Feb 25, 2022   
    All of the results as well as the use-dependence of the rosiglitazone-mediated blockade indicate that rosiglitazone acts on Kv1.5 channels as an open channel blocker. This study suggests that the cardiac side effects of rosiglitazone might be mediated in part by suppression of Kv1.5 channels, and therefore, raises a concern of using the drug for diabetic therapeutics.
  • ||||||||||  Review, Journal:  Peptide Inhibitors of Kv1.5: An Option for the Treatment of Atrial Fibrillation. (Pubmed Central) -  Dec 29, 2021   
    We found two peptides in the literature, which inhibited I: Ts6 and Osu1. Their affinity and selectivity for Kv1.5 can be improved by rational drug design in which their amino acid sequences could be modified in a targeted way guided by in silico docking experiments.
  • ||||||||||  Journal:  Chemical and Biological Study of Novel Aplysiatoxin Derivatives from the Marine Cyanobacterium Lyngbya sp. (Pubmed Central) -  Jul 11, 2021   
    While neo-aplysiatoxins (neo-ATXs) did not exhibit apparent brine shrimp toxicity, but showed potent blocking action against potassium channel Kv1.5, likewise, compounds 1 and 2 with IC values of 1.79 ± 0.22 µM and 1.46 ± 0.14 µM, respectively. Therefore, much of the current knowledge suggests the ATXs with different structure modifications may modulate multiple cellular signaling processes in animal systems leading to the harmful effects on public health.
  • ||||||||||  Journal:  Selective expression of KCNA5 and KCNB1 genes in gastric and colorectal carcinoma. (Pubmed Central) -  May 13, 2021   
    Inhibition of the Kv current with darifenacin occurred by shifting the steady-state activation and inactivation curves regardless of its anti-muscarinic effect. The data highlight, for the first time, the potential role of Kv1.5 and Kv2.1 in gastrointestinal-related cancers and suggests they may be promising prognostic markers for these tumours.
  • ||||||||||  Journal:  Non-dioxin-like polychlorinated biphenyl 19 has distinct effects on human Kv1.3 and Kv1.5 channels. (Pubmed Central) -  May 12, 2021   
    Regarding the Kv1.5 channel, PCB19 affected neither the peak current nor the steady-state current at the same concentrations tested in the Kv1.3 experiments, showing selective inhibition of PCB19 on the Kv1.3 than the Kv1.5. The presented data indicate that PCB19 could acutely affect the human Kv1.3 channel through a non-genomic mechanism, possibly causing toxic effects on various human physiological functions related to the Kv1.3 channel, such as immune and neural systems.
  • ||||||||||  Preclinical, Journal:  Selective blocking of CXCR2 prevents and reverses atrial fibrillation in spontaneously hypertensive rats. (Pubmed Central) -  May 7, 2021   
    These effects were associated with the inhibition of multiple signalling pathways, including TGF-β1/Smad2/3, NF-κB-P65, NOX1, NOX2, Kir2.1, Kv1.5 and Cx43. In conclusion, this study provides new evidence that blocking CXCR2 prevents and reverses the development of AF in SHRs, and suggests that CXCR2 may be a potential therapeutic target for hypertensive AF.
  • ||||||||||  semaxanib (SU5416) / Pfizer
    Journal:  Uncovered Contribution of Kv7 Channels to Pulmonary Vascular Tone in Pulmonary Arterial Hypertension. (Pubmed Central) -  May 1, 2021   
    Using the patch-clamp technique, we found that the total K current is reduced in PA smooth muscle cells from pulmonary hypertension animals (SU5416 plus hypoxia) and Kv7 currents made a higher contribution to the net K current...Therefore, compared with other downregulated channels, the contribution of Kv7 channels is increased in PAH resulting in an enhanced sensitivity to Kv7 channel modulators. This study provides insight into the potential usefulness of targeting Kv7 channels in PAH.
  • ||||||||||  Journal:  K1.5-Kβ1.3 Recycling Is PKC-Dependent. (Pubmed Central) -  Apr 17, 2021   
    Live cell imaging indicated that PKC inhibition almost abolished the recycling of the K1.5-Kβ1.3 channels, generating an accumulation of channels into the cytoplasm. All these results suggest that the trafficking regulation of K1.5-Kβ1.3 channels is dependent on phosphorylation by PKC and, therefore, they could represent a clinically relevant issue, mainly in those diseases that exhibit modifications in PKC activity.
  • ||||||||||  Journal:  Aging Disrupts Normal Time-of-day Variation in Cardiac Electrophysiology. (Pubmed Central) -  Mar 16, 2021   
    No time-of-day changes in expression or phosphorylation of Ca handling proteins (SERCA2, RyR2 and PLB) was found in ex vivo perfused adult isolated hearts. Conclusions - Isolated adult hearts have strong time-of-day variation in cardiac electrophysiology, Ca handling, and adrenergic responsiveness, which is disrupted with age.
  • ||||||||||  Preclinical, Journal:  Potassium Channels Kv1.3 and Kir2.1 But Not Kv1.5 Contribute to BV2 Cell Line and Primary Microglial Migration. (Pubmed Central) -  Mar 7, 2021   
    The mice were subjected to a spared nerve injury model of pain and we found that microglia motility in an 8 µm insert was reduced 2 days after spared nerve injury (SNI) compared with sham conditions. Additional investigations showed a further impact on cell motility by specifically blocking Kv1.3 and Kir2.1 but not Kv1.5; (4) Our study highlights the importance of the Kv1.3 and Kir2.1 but not Kv1.5 potassium channels on microglia migration both in BV2 and primary cell cultures.
  • ||||||||||  Jardiance (empagliflozin) / Eli Lilly, Boehringer Ingelheim
    Journal:  Empagliflozin dilates the rabbit aorta by activating PKG and voltage-dependent K channels. (Pubmed Central) -  Jan 7, 2021   
    Application of nifedipine (L-type Ca channel inhibitor) or thapsigargin (sarco-endoplasmic reticulum Ca-ATPase pump inhibitor) did not impact empagliflozin-induced vasodilation. Therefore, empagliflozin induces vasodilation by activating PKG and Kv channels.
  • ||||||||||  Review, Journal:  Voltage-Gated Potassium Channels as Regulators of Cell Death. (Pubmed Central) -  Jan 1, 2021   
    In turn, these factors affect cell cycle progression, proliferation and apoptosis. The present review summarizes our current knowledge about the involvement of various voltage-gated channels of the Kv family in the above processes and discusses the possibility of their pharmacological targeting in the context of cancer with special emphasis on Kv1.1, Kv1.3, Kv1.5, Kv2.1, Kv10.1, and Kv11.1.
  • ||||||||||  Journal:  Aberrant cardiac metabolism leads to cardiac arrhythmia. (Pubmed Central) -  Nov 21, 2020   
    Here, I discuss metabolic genes, enzymes and reducing equivalents and functional aspects of metabolic-induced arrhythmia with a special focus on atrial induced arrhythmia. It appears that normalisation of altered Kv1.5 channel, an oxygen sensing ion channel and fulfillment of oxygen demand by myocardium might offer a new strategy for preventing alterations of repolarisation that cause arrhythmia.
  • ||||||||||  doxycycline / Generic mfg., Pierre Fabre
    [VIRTUAL] Increased Myofilament Calcium Sensitivity Drives Focal Ischemia and Ventricular Arrhythmias in Hypertrophic Cardiomyopathy (OnDemand) -  Sep 22, 2020 - Abstract #AHA2020AHA_4519;    
    To test whether counteracting focal ischemia in I79N hTnT Tg mice by increasing blood flow would attenuate pacing-induced VEAs, we crossed smooth muscle-specific doxycycline (Dox) inducible Kv1.5 channel and I79N hTnT Tg mice...We conclude that focal ischemia and VEAs in HCM are both fundamentally determined by altered myofilament Ca2+ sensitivity, and that increasing coronary blood flow within the I79N hTnT HCM substrate counteracts the focal ischemia and VEAs induced by myofilament Ca2+ sensitization. These findings provide a novel mechanistic understanding of the basis for VEAs in HCM, and have translational implications for both prognostication and the development of blood flow-modulation approaches to antiarrhythmic therapy in HCM.
  • ||||||||||  Review, Journal:  Challenges Faced with Small Molecular Modulators of Potassium Current Channel Isoform Kv1.5. (Pubmed Central) -  Sep 16, 2020   
    SAR analysis is regarded as a useful strategy in structural elucidation, as it relates to the characteristics that improve compounds targeting Kv1.5. Herein, we present previous studies regarding the structural, pharmacological, and SAR information of the Kv1.5 modulator, through which we can assist in identifying and designing potent and specific Kv1.5 inhibitors in the treatment of diseases involving Kv1.5 activity.
  • ||||||||||  Review, Journal:  A Novel Treatment for Arrhythmias via the Control of the Degradation of Ion Channel Proteins. (Pubmed Central) -  Sep 5, 2020   
    As a result, ion channel proteins are not transported to the cell membrane and are involved in the development of atrial fibrillation. This review takes the Kv1.5 channel as an example and focuses on the degradation mechanism of ion channel proteins, and discusses its application to the treatment of arrhythmia by drugs that control the mechanism of ion channel protein degradation.
  • ||||||||||  dalfampridine / Generic mfg.
    Journal:  Ultrarapid Delayed Rectifier K Channelopathies in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes. (Pubmed Central) -  Aug 28, 2020   
    Native I, measured as current sensitive to 50 μM 4-aminopyridine, was 1.88 ± 0.49 (mean ± SEM, n = 17) and 0.26 ± 0.26 pA/pF (n = 17) in atrial- and ventricular-like hiPSC-CMs, respectively...We conclude that a decrease in I, mimicking loss-of-function mutations, has a stronger effect on the AP of hiPSC-CMs than an increase, mimicking gain-of-function mutations, whereas in ventricular-like hiPSC-CMs such increase results in AP shortening, causing their AP morphology to become more atrial-like. Effects of native I modulation on atrial-like hiPSC-CMs are less pronounced than effects of virtual I injection because I density of atrial-like hiPSC-CMs is substantially smaller than that of freshly isolated human atrial myocytes.
  • ||||||||||  Journal:  Structural basis of the potency and selectivity of Urotoxin, a potent Kv1 blocker from scorpion venom. (Pubmed Central) -  Aug 27, 2020   
    Docking analysis was consistent with occlusion of the pore by K25 and the requirement of a small, non-charged amino acid in the Kv1 channel vestibule to facilitate toxin-channel interactions. Finally, computational studies revealed key interactions between the amidated C-terminus of Urotoxin and a conserved Asp residue in the turret of Kv1 channels, offering a potential rationale for potency differences between native and recombinant Urotoxin.
  • ||||||||||  Journal:  Studies of Conorfamide-Sr3 on Human Voltage-Gated Kv1 Potassium Channel Subtypes. (Pubmed Central) -  Aug 24, 2020   
    CNF-Sr3 showed a 10 times higher affinity for the Kv1.6 subtype with respect to Kv1.3 (IC = 2.7 and 24 μM, respectively) and no significant effect on Kv1.4 and Kv1.5 at 10 µM. Thus, CNF-Sr3 might become a novel molecular probe to study diverse aspects of human Kv1.3 and Kv1.6 channels.