Publications by authors named "GongXin Liu"

Heart failure (HF) and cardiac arrhythmias share overlapping pathological mechanisms that act cooperatively to accelerate disease pathogenesis. Cardiac fibrosis is associated with both pathological conditions. Our previous work identified a link between phytosterol accumulation and cardiac injury in a mouse model of phytosterolemia, a rare disorder characterized by elevated circulating phytosterols and increased cardiovascular disease risk.

View Article and Find Full Text PDF

The physiological role of cardiac late Na current ( I) has not been well described. In this study, we tested the hypothesis that selective inhibition of physiological late I abbreviates the normal action potential (AP) duration (APD) and counteracts the prolongation of APD and arrhythmic activities caused by inhibition of the delayed rectifier K current ( I). The effects of GS-458967 (GS967) on the physiological late I and APs in rabbit isolated ventricular myocytes and on the monophasic APs and arrhythmias in rabbit isolated perfused hearts were determined.

View Article and Find Full Text PDF

Late sodium current (late I) is enhanced during ischemia by reactive oxygen species (ROS) modifying the Na 1.5 channel, resulting in incomplete inactivation. Compound 4 (GS-6615, eleclazine) a novel, potent, and selective inhibitor of late I, is currently in clinical development for treatment of long QT-3 syndrome (LQT-3), hypertrophic cardiomyopathy (HCM), and ventricular tachycardia-ventricular fibrillation (VT-VF).

View Article and Find Full Text PDF

Background And Purpose: Enhanced late Na current (late I ) in the myocardium is pro-arrhythmic. Inhibition of this current is a promising strategy to stabilize ventricular repolarization and suppress arrhythmias. Here, we describe GS-6615, a selective inhibitor of late I , already in clinical development for the treatment of long QT syndrome 3 (LQT3).

View Article and Find Full Text PDF

Background: Remodeling of cardiac repolarizing currents, such as the downregulation of slowly activating K+ channels (IKs), could underlie ventricular fibrillation (VF) in heart failure (HF). We evaluated the role of Iks remodeling in VF susceptibility using a tachypacing HF model of transgenic rabbits with Long QT Type 1 (LQT1) syndrome.

Methods And Results: LQT1 and littermate control (LMC) rabbits underwent three weeks of tachypacing to induce cardiac myopathy (TICM).

View Article and Find Full Text PDF

Introduction: Ventricular rate during atrial fibrillation (AF) can be reduced by slowing atrioventricular (AV) node conduction and/or by decreasing dominant frequency of AF. We investigated whether combined administration of ivabradine and ranolazine reduces ventricular rate during AF.

Methods And Results: Ivabradine (maximum clinical dose, 0.

View Article and Find Full Text PDF

Background: If channels are functionally expressed in atrioventricular (AV) nodal tissue.

Objective: The purpose of this study was to address whether the prototypical If inhibitor, ivabradine, at clinically safe concentrations can slow AV node conduction to reduce ventricular rate (VR) during atrial fibrillation (AF).

Methods: Effects of ivabradine (0.

View Article and Find Full Text PDF

Inhibition of cardiac late Na(+) current (I(Na,L)) decreases sodium-dependent calcium overload in diseased hearts. Because INa,L is small in the absence of disease, its inhibition is not expected to significantly alter function of the normal heart. To test this hypothesis, we determined the effects of GS-458967 (GS967), a novel selective inhibitor of I(Na,L) (IC(50) = 0.

View Article and Find Full Text PDF

Inhibition of cardiac late sodium current (late I(Na)) is a strategy to suppress arrhythmias and sodium-dependent calcium overload associated with myocardial ischemia and heart failure. Current inhibitors of late I(Na) are unselective and can be proarrhythmic. This study introduces GS967 (6-[4-(trifluoromethoxy)phenyl]-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine), a potent and selective inhibitor of late I(Na), and demonstrates its effectiveness to suppress ventricular arrhythmias.

View Article and Find Full Text PDF

Early after-depolarization (EAD), or abnormal depolarization during the plateau phase of action potentials, is a hallmark of long-QT syndrome (LQTS). More than 13 genes have been identified as responsible for LQTS, and elevated risks for EADs may depend on genotypes, such as exercise in LQT1 vs. sudden arousal in LQT2 patients.

View Article and Find Full Text PDF

In contrast to the other heterotrimeric GTP-binding proteins (G proteins) Gs and Gi, the functional role of G o is still poorly defined. To investigate the role of G alpha o in the heart, we generated transgenic mice with cardiac-specific expression of a constitutively active form of G alpha o1* (G alpha o*), the predominant G alpha o isoform in the heart. G alpha o expression was increased 3- to 15-fold in mice from 5 independent lines, all of which had a normal life span and no gross cardiac morphological abnormalities.

View Article and Find Full Text PDF

Cardiac ATP-sensitive K+ (K(ATP)) channels are formed by Kir6.2 and SUR2A subunits. We produced transgenic mice that express dominant negative Kir6.

View Article and Find Full Text PDF

KCa3.1 is an intermediate conductance Ca2+-activated K+ channel that is expressed predominantly in hematopoietic cells, smooth muscle cells, and epithelia where it functions to regulate membrane potential, Ca2+ influx, cell volume, and chloride secretion. We recently found that the KCa3.

View Article and Find Full Text PDF

Myotubularins (MTMs) belong to a large subfamily of phosphatases that dephosphorylate the 3' position of phosphatidylinositol 3-phosphate [PI(3)P] and PI(3,5)P(2). MTM1 is mutated in X-linked myotubular myopathy, and MTMR2 and MTMR13 are mutated in Charcot-Marie-Tooth syndrome. However, little is known about the general mechanism(s) whereby MTMs are regulated or the specific biological processes regulated by the different MTMs.

View Article and Find Full Text PDF

The targeting of ion channels to particular membrane microdomains and their organization in macromolecular complexes allow excitable cells to respond efficiently to extracellular signals. In this study, we describe the formation of a complex that contains two scaffolding proteins: caveolin-3 (Cav-3) and a membrane-associated guanylate kinase (MAGUK), SAP97. Complex formation involves the association of Cav-3 with a segment of SAP97 localized between its PDZ2 and PDZ3 domains.

View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_session3itc49uu7dp2cmlcm7uof0qr7c2r71r5): Failed to open stream: No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 177

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)

Filename: Session/Session.php

Line Number: 137

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once