A5101423607- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Neuroscience and Neural Engineering
- Cardiomyopathy and Myosin Studies
- Receptor Mechanisms and Signaling
- Cardiac pacing and defibrillation studies
- Acute Myeloid Leukemia Research
- Cardiovascular Effects of Exercise
- Peptidase Inhibition and Analysis
- Mitochondrial Function and Pathology
- Fatty Acid Research and Health
- ATP Synthase and ATPases Research
- Nicotinic Acetylcholine Receptors Study
- Platelet Disorders and Treatments
- Blood groups and transfusion
- Mass Spectrometry Techniques and Applications
- Electrostatic Discharge in Electronics
- Glycosylation and Glycoproteins Research
- Blood transfusion and management
- Autophagy in Disease and Therapy
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Abdominal Trauma and Injuries
- Redox biology and oxidative stress
- RNA and protein synthesis mechanisms
Soochow University
2024
First Affiliated Hospital of Soochow University
2024
Chinese Academy of Medical Sciences & Peking Union Medical College
2005-2022
Nantong University
2022
Weatherford College
2022
Taizhou People's Hospital
2022
Virginia Commonwealth University
2010-2021
Shandong University
2020
Beijing Tongren Hospital
2019
Peking Union Medical College Hospital
2018
Abstract —Inherited mutations and a polymorphism in minK-related peptide 1 (MiRP1) have been linked to congenital or acquired long-QT syndrome, pointing the importance of MiRP1 maintaining cardiac electrical stability. We tested whether could affect function Kv4.x (x=2 3), major pore-forming (α) subunits transient outward ( I ) channels heart. used Xenopus oocyte expression system examine effects on channel gating kinetics current amplitude correlated these with level. slowed rates Kv4.2...
The compound 3,3′,4′,5,5′,7-hexahydroxyflavone (myricetin) is a natural flavonoid with antitumour activity. Most of the studies on myricetin have focused induction tumour cell apoptosis, and little known about regulatory effects autophagy in colorectal cancer. Here, we studied colon cancer proliferation, apoptosis autophagy. We detected induced by via flow cytometry Hoechst 33258 staining. Transmission electron microscopy was performed to observe morphological changes associated expression...
C-type inactivation in the HERG channel is unique among voltage-gated K channels having extremely fast kinetics and strong voltage sensitivity. This suggests that may have a outer mouth structure (where conformational changes underlie inactivation), and/or communication between sensor. We use cysteine-scanning mutagenesis thiol-modifying reagents to probe structural functional role of S5-P (residues 571–613) P-S6 631–638) linkers line vestibule channel. Disulfide formation involving...
The goals of this study are to investigate the mechanism and site action whereby a human ether-a-go-go-related gene (HERG)-specific scorpion peptide toxin, ErgTx, suppresses HERG current. We apply cysteine-scanning mutagenesis S5-P P-S6 linkers examine resulting changes in ErgTx potency. Data compared with characteristics charybdotoxin (ChTx, or its analogs) binding Shaker channel. binds outer vestibule but may not physically occlude pore. In contrast ChTx. interaction, elevating [K](o)...
KCNQ1 and KCNE1 (Q1 E1) associate to form the slow delayed rectifier IKs channels in heart. A short stretch of eight amino acids at extracellular end S1 Q1 (positions 140–147) harbors six arrhythmia-associated mutations. Some these mutations affect channel function only when coexpressed with E1, suggesting that this region may engage interaction E1 critical for function. Identifying Q1/E1 contact points here provide new insights into how operates. We focus on position 145 positions 40–43....
Objective: The rapid (IKr) and slow (IKs) components of delayed rectifier currents play an important role in determining the cardiac action potential configuration. Abnormalities their function may contribute to arrhythmogenesis under pathological conditions. We studied effects myocardial infarction on IKr IKs canine ventricular myocytes molecular basis. Methods: Infarct zone (IZs) were isolated from a thin layer surviving epicardium overlying infarct 5 days after total occlusion left...
Mutations in KCNE2 have been linked to long-QT syndrome (LQT6), yet protein expression the ventricle and its functional role native channels are not clear.We detected human, dog, rat ventricles Western blot experiments. Immunocytochemistry confirmed ventricular myocytes. To explore of KCNE2, we studied how was altered 2 models cardiac pathology whether these alterations could help explain observed changes function channels, for which is a putative auxiliary (beta) subunit. In canine injured...
The transmembrane domains of HERG (S1–S3) contain six negative charges: three are conserved in all voltage-gated K channels (D456 and D466 S2, D501 S3) unique to the EAG family (D411 S1, D460 D509 S3). We infer functional role these aspartates by studying how substituting them with cysteine, one at a time, affects channel function. D456C is not functional, suggesting that this charge may play critical protein folding during biogenesis, as has been shown for its counterpart Shaker channel....
The hERG channel has an unusually long 'S5-P linker' (residues 571-613) that lines the outer mouth of pore. Previously, we have shown residues along this S5-P linker are critical for fast-inactivation process and K(+) selectivity channel. Here used several approaches to probe structure its interactions with other domains Circular dichroism NMR analysis a synthetic peptide suggested is quite dynamic: central region (positions 583-593) can be unstructured or helical, depending on whether it...
Kv4/K channel-interacting protein (KChIP) potassium channels are a major class of rapidly inactivating K in brain and heart. Considering the importance alternative splicing to quantitative features KChIP gating modulation, previously uncharacterized splice form KChIP1 was functionally characterized. The KChIP1b variant differs from characterized KChIP1a by inclusion novel amino-terminal region that is encoded an exon conserved mouse, rat, human genes. expression mRNA high but undetectable...
The fast-inactivation process in the hERG channel can be affected by mutations pore or S6 domain, similar to C-type inactivation Shaker channel. However, differences kinetics and voltage dependence of between these two channels suggest that different structural determinants may involved. To explore this possibility, we mutated a serine outer mouth region (S631) residues physicochemical properties compared resulting changes channel's with those from an equivalent position (T449). most...
Azimilide (AZ) is a class III antiarrhythmic drug that has voltage-dependent dual effects on the HERG channel: 1) increasing current amplitude at low-voltage depolarization (agonist effect), and 2) suppressing more depolarized voltages (antagonist effect). We examined mechanism for agonist effect of AZ expressed in Xenopus oocytes. The resulted from an AZ-induced 'prepulse potentiation: strong prepulse increased rate degree channel activation induced by subsequent to -50 or -40 mV....