A5087985631- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Neuroscience and Neuropharmacology Research
- Neuroscience and Neural Engineering
- Cardiomyopathy and Myosin Studies
- Receptor Mechanisms and Signaling
- Fibroblast Growth Factor Research
- Cardiovascular Effects of Exercise
- Neural dynamics and brain function
- Photoreceptor and optogenetics research
- Cardiovascular Function and Risk Factors
- Circadian rhythm and melatonin
- Photochromic and Fluorescence Chemistry
- Nicotinic Acetylcholine Receptors Study
- Cardiac Arrhythmias and Treatments
- Nitric Oxide and Endothelin Effects
- Congenital heart defects research
- Connective tissue disorders research
- Mitochondrial Function and Pathology
- Erythrocyte Function and Pathophysiology
- Fuel Cells and Related Materials
- RNA Research and Splicing
- Atrial Fibrillation Management and Outcomes
- RNA modifications and cancer
- Neurobiology and Insect Physiology Research
Washington University in St. Louis
2015-2024
John Cochran VA Medical Center
2019
National Taiwan University
2014-2018
National Taiwan University Hospital
2018
University of Chicago
2018
Institute of Developmental Physiology
2010-2017
University of Iowa
2001-2017
University of Illinois Chicago
2017
Universitäts-Herzzentrum Freiburg-Bad Krozingen
2016
Imperial College London
2016
D espite the significant decline in coronary artery disease (CAD) mortality second half of 20th century, 1 sudden cardiac death (SCD) continues to claim 250 000 300 US lives annually. 24][5][6] Because absence emergency medical response systems most world regions, worldwide estimates are currently not available. 7However, even presence advanced first responder for resuscitation out-of-hospital arrest, overall survival rate a recent North American analysis was 4.6%. 8SCD can manifest as...
Abstract —Chronic atrial fibrillation (AF) is characterized by decreased contractility, shortened action potential duration, and accommodation of duration to changes in activation rate. Studies on experimental animal models AF implicate a reduction L-type Ca 2+ current ( I ) density these changes. To evaluate the effect human , we compared myocytes isolated from 42 patients normal sinus rhythm at time cardiac surgery with that 11 chronic patients. was significantly reduced (mean −3.35±0.5...
Chronic atrial fibrillation is associated with a shortening of the action potential duration and refractory period. To test hypothesis that these changes are mediated by in density specific K+ currents, we compared currents left right myocytes delayed rectifier channel alpha-subunit proteins (Kv1.5 Kv2.1) appendages from patients (n = 28) normal sinus rhythm those 15) chronic (AF). Contrary to our expectations, nystatin-perforated patch recordings whole-cell revealed significant reductions...
To explore the role of peroxisome proliferator-activated receptor α (PPARα)-mediated derangements in myocardial metabolism pathogenesis diabetic cardiomyopathy, insulinopenic mice with PPARα deficiency (PPARα −/− ) or cardiac-restricted overexpression [myosin heavy chain (MHC)-PPAR] were characterized. Whereas protected from development diabetes-induced cardiac hypertrophy, combination diabetes and MHC-PPAR genotype resulted a more severe cardiomyopathic phenotype than either did alone....
Evidence is emerging that systemic metabolic disturbances contribute to cardiac myocyte dysfunction and clinically apparent heart failure, independent of associated coronary artery disease. To test the hypothesis perturbation lipid homeostasis in cardiomyocytes contributes dysfunction, we engineered transgenic mice with cardiac-specific overexpression fatty acid transport protein 1 (FATP1) using α-myosin heavy chain gene promoter. Two lines demonstrate 4-fold increased myocardial free (FFA)...
Microarrays have been used extensively to profile transcriptome remodeling in failing human heart, although the genomic coverage provided is limited and fails provide a detailed picture of myocardial landscape. Here, we describe sequencing-based profiling, providing comprehensive analysis mRNA, microRNA (miRNA), long noncoding RNA (lncRNA) expression heart before after mechanical support with left ventricular (LV) assist device (LVAD). Deep sequencing isolated from paired nonischemic (NICM;...
MicroRNA (miR)-133a regulates cardiac and skeletal muscle differentiation plays an important role in development. Because miR-133a levels decrease during reactive hypertrophy, some have considered that restoring could suppress hypertrophic remodeling.To prevent the "normal" downregulation of induced by acute stimulus adult heart.miR-133a is downregulated transverse aortic constriction (TAC) isoproterenol-induced but not 2 genetic hypertrophy models. Using MYH6 promoter-directed expression a...
Rationale: Mitochondrial Ca 2+ uptake is essential for the bioenergetic feedback response through stimulation of Krebs cycle dehydrogenases. Close association mitochondria to sarcoplasmic reticulum (SR) may explain efficient mitochondrial despite low affinity uniporter. However, existence such microdomains and their functional role are presently unresolved. Mitofusin (Mfn) 1 2 mediate outer membrane fusion, whereas Mfn2 but not Mfn1 tethers endoplasmic in noncardiac cells. Objective: To...
In the experiments here, time- and voltage-dependent properties of Ca2+-independent, depolarization-activated K+ currents in adult mouse ventricular myocytes were characterized detail. majority (65 72, ≈ 90%) cells dispersed from ventricles, analysis decay phases outward revealed three distinct current components: a rapidly inactivating, transient current, Ito,f (mean ± SEM τdecay = 85 2 ms); slowly 1,162 29 ms) inactivating IK,slow; non steady state Iss. small subset (7 10%) cells, was...
Depolarization-activated outward K+ currents in isolated adult rat ventricular myocytes were characterized using the whole-cell variation of patch-clamp recording technique. During brief depolarizations to potentials positive -40 mV, Ca(2+)-independent these cells rise a transient peak, followed by slower decay an apparent plateau. The analyses completed here reveal that observed current waveforms result from activation two kinetically distinct voltage-dependent currents: one activates and...
A novel in vivo experimental strategy, involving cell type-specific expression of a dominant-negative K+ channel pore-forming alpha subunit, was developed and exploited to probe the molecular identity cardiac transient outward current (I(to)). point mutation (W F) introduced at position 362 pore region Kv4.2 produce nonconducting mutant (Kv4.2W362F) subunit. Coexpression Kv4.2W362F with (or Kv4.3) attenuates wild-type currents, effect is subfamily specific; ie, does not affect heterologously...
The National Heart, Lung, and Blood Institute Office of Rare Diseases at the Institutes Health organized a workshop (September 14 to 15, 2006, in Bethesda, Md) advise on new research directions needed for improved identification treatment rare inherited arrhythmias. These included following: (1) Na+ channelopathies; (2) arrhythmias due K+ channel mutations; (3) other arrhythmogenic mechanisms. Another major goal was provide recommendations support, enable, or facilitate improve future...
Abstract Polyclonal antibodies against each of the K + channel subunits (Kv1.2, Kv1.4, Kv1.5, Kv2.1, and Kv4.2) shown previously to be expressed in adult rat heart at mRNA level were used examine distributions these atrial ventricular membranes. Immunohistochemistry on isolated myocytes revealed strong labeling with anti-Kv4.2 anti-Kv1.2 antibodies. Although somewhat weaker (than or anti-Kv4.2), positive staining was also observed anti-Kv1.5 anti-Kv2.1 Ventricular exposed anti-Kv1.4...
Cellular K+ efflux is a requisite event in the unfolding of apoptosis programs across many types cells and death-inducing stimuli; however, molecular identities ion channels mediating this key have remained undefined. Here, we show that Kv2.1-encoded are responsible for expression cortical neurons vitro. Transient two different dominant-negative forms subunit completely eliminated enhancement currents normally accompanies cell death process. Importantly, deficient functional were protected...
The low density lipoprotein receptor-related protein (LRP) is a multifunctional cell surface receptor, expressed in liver, that binds with high affinity and endocytoses several structurally functionally distinct ligands, including apolipoprotein E-activated /3-migrating very lipoprotein, tissue-type plasminogen activator, or,-macroglobulin.Here using situ hybridization quantitative RNase protection assays, we show LRP also throughout the brain.LRP message particularly cerebellum, cortex,...
The effects of alpha 1-adrenergic agonists on the waveforms action potentials and voltage-gated ionic currents were examined in isolated adult rat ventricular myocytes by whole-cell patch-clamp recording technique. After "puffer" applications either two 1 agonists, phenylephrine methoxamine, action-potential durations increased. In voltage-clamped cells, (5-20 microM) or methoxamine (5-10 reduced amplitudes Ca2+-independent voltage-activated outward K+ (Iout); neither kinetics nor...