Open channel block of Kv1.5 channels by HMQ1611.

Kv1.5 channels conduct the ultra-rapid delayed rectifier potassium current ( ). Pharmacological blockade of human Kv1.

Propofol, an Anesthetic Agent, Inhibits HCN Channels through the Allosteric Modulation of the cAMP-Dependent Gating Mechanism.

Propofol is a broadly used intravenous anesthetic agent that can cause cardiovascular effects, including bradycardia and asystole. A possible mechanism for these effects is slowing cardiac pacemaker activity due to inhibition of the hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels. However, it remains unclear how propofol affects the allosteric nature of the voltage- and cAMP-dependent gating mechanism in HCN channels.

Expression and functional maintenance of volume-regulated anion channels in myometrial smooth muscles of pregnant mice.

Pregnancy causes changes in the uterus, such as increased cell volume and altered water content. However, the mechanisms that protect the structure and maintain the function of uterine smooth muscle cells against these changes during pregnancy have not been clarified. This study focused on the volume-regulated anion channel (VRAC), which opens with cell swelling under low osmotic pressure and releases Cl ions and various organic osmolytes to resist cell swelling and regulates a wide range of biological processes such as cell death.

Dexmedetomidine Exerts a Negative Chronotropic Action on Sinoatrial Node Cells Through the Activation of Imidazoline Receptors.

Dexmedetomidine (DEX), an α2-adrenoreceptor (α2-AR) and imidazoline receptor agonist, is most often used for the sedation of patients in the intensive care unit. Its administration is associated with an increased incidence of bradycardia; however, the precise mechanism of DEX-induced bradycardia has yet to be fully elucidated. This study was undertaken to examine whether DEX modifies pacemaker activity and the underlying ionic channel function through α2-AR and imidazoline receptors.

Selective activation of adrenoceptors potentiates I current in pulmonary vein cardiomyocytes through the protein kinase A and C signaling pathways.

Delayed rectifier K current (I) is a key contributor to repolarization of action potentials. This study investigated the mechanisms underlying the adrenoceptor-induced potentiation of I in pulmonary vein cardiomyocytes (PVC). PVC were isolated from guinea pig pulmonary vein.

Open-channel blocking action of volatile anaesthetics desflurane and sevoflurane on human voltage-gated K 1.5 channel.

Background And Purpose: Volatile anaesthetics have been shown to differentially modulate mammalian Shaker-related voltage-gated potassium (K 1.x) channels. This study was designed to investigate molecular and cellular mechanisms underlying the modulatory effects of desflurane or sevoflurane on human K 1.

Vildagliptin Versus α-Glucosidase Inhibitor as Add-On to Metformin for Type 2 Diabetes: Subgroup Analysis of the China Prospective Diabetes Study.

Introduction: The effect of dipeptidyl peptidase-4 (DDP-4) inhibitors versus α-glucosidase inhibitors (AGIs) on the treatment of type 2 diabetes mellitus (T2DM) in a real-world setting is unknown. The aim of this real-world study was to compare the glucose-lowering effect and tolerability of vildagliptin as add-on to metformin monotherapy (VM) and AGI as add-on to metformin monotherapy (AM) in Chinese patients with T2DM.

Methods: This was a subgroup analysis of the China Prospective Diabetes Study, a post-marketing, prospective, observational, real-world study conducted at 52 centers in China.

A de novo gain-of-function KCND3 mutation in early repolarization syndrome.

Background: Early repolarization syndrome (ERS) is characterized by J-point elevation on electrocardiograms and ventricular fibrillation (VF). Early repolarization arises from augmentation of the transmural electrical gradient in the cardiac action potential; therefore, the transient outward potassium current (I) has been regarded as a key candidate current for elucidating the mechanism of ERS. KCND3 encoding Kv4.

Identification of Verapamil Binding Sites Within Human Kv1.5 Channel Using Mutagenesis and Docking Simulation.

Background/aims: The phenylalkylamine class of L-type Ca channel antagonist verapamil prolongs the effective refractory period (ERP) of human atrium, which appears to contribute to the efficacy of verapamil in preventing reentrant-based atrial arrhythmias including atrial fibrillation. This study was designed to investigate the molecular and electrophysiological mechanism underlying the action of verapamil on human Kv1.5 (hKv1.

Erratum: Combined antitumor effects of P-5m octapeptide and 5- fluorouracil on a murine model of H22 hepatoma ascites.

[This corrects the article DOI: 10.3892/etm.2018.

Combined antitumor effects of P-5m octapeptide and 5-fluorouracil on a murine model of H22 hepatoma ascites.

The present study has demonstrated that P-5m octapeptide (P-5m) has therapeutic potential in metastatic human hepatocarcinoma, possibly through the modulation of matrix metalloproteinase-2 expression. The purpose of the present study was to evaluate the antitumor effect of P-5m combined with 5-fluorouracil (5-Fu) on the treatment of hepatoma 22 (H22) hepatocarcinoma malignant ascites in a mouse model. The inhibitory effect on the growth of mouse ascites tumors was monitored by measuring body weight gain, survival time, ascites volume, numbers of tumor cells, DNA synthesis and peritoneal capillary permeability analysis.

A hERG mutation E1039X produced a synergistic lesion on I together with KCNQ1-R174C mutation in a LQTS family with three compound mutations.

Congenital long QT syndrome (LQTS) caused by compound mutations is usually associated with more severe clinical phenotypes. We identified a LQTS family harboring three compound mutations in different genes (KCNQ1-R174C, hERG-E1039X and SCN5A-E428K). KCNQ1-R174C, hERG-E1039X and SCN5A-E428K mutations and/or relevant wild-type (WT) cDNAs were respectively expressed in mammalian cells.

Transient Receptor Potential Canonical Channel Blockers Improve Ventricular Contractile Functions After Ischemia/Reperfusion in a Langendorff-perfused Mouse Heart Model.

Reperfusion of ischemic myocardium is accompanied by intracellular Ca overload, leading to cardiac dysfunction. However, the mechanisms underlying intracellular Ca overload have yet to be fully elucidated. The mechanism may involve the activation of store-operated Ca entry, which is primarily mediated through the transient receptor potential canonical (TRPC) channels.

Interactions of Propofol With Human Voltage-gated Kv1.5 Channel Determined by Docking Simulation and Mutagenesis Analyses.

Propofol blocks the voltage-gated human Kv1.5 (hKv1.5) channel by preferentially affecting in its open state.

Heterogeneous functional expression of the sustained inward Na current in guinea pig sinoatrial node cells.

The sustained inward Na current (I ) identified in the sinoatrial node (SAN) cell has been suggested to play a pivotal role in cardiac pacemaking. However, the composition of cells in the SAN is heterogeneous and cell-to-cell variability in the magnitude of I remains to be fully characterized. The present study investigated the current density of I in morphologically different types of pacemaker cells dissociated from guinea pig SAN.

Novel intracellular transport-refractory mutations in KCNH2 identified in patients with symptomatic long QT syndrome.

Background: Missense mutations in KCNH2, a gene encoding the Kv11.1 channel, cause long QT syndrome (LQTS) type 2 primarily by disrupting the intracellular transport of Kv11.1 to the plasma membrane.

Ca1.3 L-type Ca channel contributes to the heartbeat by generating a dihydropyridine-sensitive persistent Na current.

The spontaneous activity of sinoatrial node (SAN) pacemaker cells is generated by a functional interplay between the activity of ionic currents of the plasma membrane and intracellular Ca dynamics. The molecular correlate of a dihydropyridine (DHP)-sensitive sustained inward Na current (I ), a key player in SAN automaticity, is still unknown. Here we show that I and the L-type Ca current (I ) share Ca1.

Contribution of a KCNH2 variant in genotyped long QT syndrome: Romano-Ward syndrome under double mutations and acquired long QT syndrome under heterozygote.

Background: Long QT syndrome (LQTS) presents two clinical phenotypes, congenital and acquired forms. This study aims to evaluate the genetic contribution of a KCNH2 variant for the two LQTS phenotypes.

Methods: From 1996 to 2014, genetic screening for LQTS probands was performed for five major genes: KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 and 389 probands were found to be mutation carriers.

Regulation of human cardiac Kv1.5 channels by extracellular acidification.

Human Kv1.5 channels (hKv1.5) conduct the ultra-rapid delayed rectifier potassium current (I ), which plays an important role in action potential repolarization of atrial myocytes.

Molecular pathogenesis of long QT syndrome type 1.

Long QT syndrome type 1 (LQT1) is a subtype of a congenital cardiac syndrome caused by mutation in the gene, which encodes the subunit of the slow component of delayed rectifier K current () channel. Arrhythmias in LQT1 are characterized by prolongation of the QT interval on ECG, as well as the occurrence of life-threatening cardiac events, frequently triggered by adrenergic stimuli (e.g.