A5081487282- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Neuroscience and Neural Engineering
- Cardiac Ischemia and Reperfusion
- Mitochondrial Function and Pathology
- Receptor Mechanisms and Signaling
- Advanced Proteomics Techniques and Applications
- Electrochemical Analysis and Applications
- Muscle Physiology and Disorders
- Cardiovascular Effects of Exercise
- Cardiovascular Function and Risk Factors
- Ion Channels and Receptors
- Electron Spin Resonance Studies
- Connexins and lens biology
- Cardiac Fibrosis and Remodeling
- Nitric Oxide and Endothelin Effects
- ATP Synthase and ATPases Research
- Traditional Chinese Medicine Analysis
- Trace Elements in Health
- Polyamine Metabolism and Applications
- Spaceflight effects on biology
- Advanced MRI Techniques and Applications
- Biological and pharmacological studies of plants
- RNA modifications and cancer
Rutgers, The State University of New Jersey
2015-2025
Rutgers New Jersey Medical School
2010-2024
Rutgers Health
2018
University Hospital, Newark
2008-2013
University of California, Los Angeles
2002-2009
Institute of Cardiology
2004-2008
UCLA Health
2008
Kyoto University
1996-2002
National Institute for Physiological Sciences
1994
Nankai University
1990
The synchronization of coupled oscillators plays an important role in many biological systems, including the heart. In heart diseases, cardiac myocytes can exhibit abnormal electrical oscillations, such as early afterdepolarizations (EADs), which are associated with lethal arrhythmias. A key unanswered question is how cellular EADs partially synchronize tissue, required for them to propagate. Here, we present evidence, from computational simulations and experiments isolated myocytes, that...
In the heart, oxidative stress caused by exogenous H(2)O(2) has been shown to induce early afterdepolarizations (EADs) and triggered activity impairing Na current (I(Na)) inactivation. Because activates Ca(2+)/calmodulin kinase (CaMK)II, which also impairs I(Na) inactivation promotes EADs, we hypothesized that CaMKII activation may be an important factor in EADs stress. Using patch-clamp intracellular Ca (Ca(i)) imaging Fluo-4 AM-loaded rabbit ventricular myocytes, found exposure (0.2 1...
Action potential duration (APD) restitution properties and repolarization alternans are thought to be important arrhythmogenic factors. We investigated the role of intracellular calcium (Ca2+i) cycling in regulating APD slope patch-clamped rabbit ventricular myocytes at 34 36 degrees C, using perforated or ruptured patch clamp techniques with Fura-2-AM record Ca2+i. When was measured by either standard extrastimulus (S1S2) method dynamic rapid pacing method, maximum exceeded 1 both methods,...
Oxidative stress with hydrogen peroxide (H(2)O(2)) readily promotes early afterdepolarizations (EADs) and triggered activity (TA) in isolated rat rabbit ventricular myocytes. Here we examined the effects of H(2)O(2) on arrhythmias intact Langendorff hearts using dual-membrane voltage intracellular calcium optical mapping glass microelectrode recordings. Young adult (3-5 mo, N = 25) 6) exhibited no when perfused (0.1-2 mM) for up to 3 h. However, 33 out 35 (94%) aged (24-26 mo) hearts, 0.1 mM...
Oxidative stress is linked to many pathological conditions, including ischemia, atherosclerosis and neurodegenerative disorders. The molecular mechanisms of oxidative induced pathophysiology cell death are currently poorly understood. Our present work demonstrates that by reactive oxygen species cigarette smoke extract depolarize the membrane open connexin hemichannels. Under stress, expression silencing resulted in increased reduced deaths, respectively. Morphological live/dead assays...
Intracellular Ca 2+ (Ca i ) waves are known to cause delayed afterdepolarizations (DADs), which have been associated with arrhythmias in cardiac disease states such as heart failure, catecholaminergic polymorphic ventricular tachycardia, and digitalis toxicity. Here we show that, addition DADs, also other consequences relevant arrhythmogenesis, including subcellular spatially discordant alternans (SDA, the amplitude of local transient alternates out phase different regions same cell), sudden...
Inwardly rectifying potassium (Kir) channels are gated by the interaction of their cytoplasmic regions with membrane-bound phosphatidylinositol-4,5-bisphosphate (PIP(2)). In present study, we examined how PIP(2) regulates channel availability and openings to various subconductance levels (sublevels) as well fully open state in strong inward rectifier Kir2.1 channel. Various constructs were expressed Xenopus oocytes single or macroscopic currents recorded from inside-out patches. The...
Heart failure (HF) is associated with increased arrhythmia risk and triggered activity. Abnormal Ca
Inward rectification in strong inward rectifiers such as Kir2.1 is attributed to voltage-dependent block by intracellular polyamines and Mg(2+). Block the polyamine spermine has a complex voltage dependence with shallow steep components concentration dependence. To understand mechanism, we measured macroscopic currents excised inside-out giant patches from Xenopus oocytes expressing Kir2.1, single channel COS7 cells transfected Kir2.1. We found that or increased, component of at more...
Background— Electrophysiological changes promoting arrhythmias during acute regional ischemia/reperfusion are challenging to study in intact cardiac tissue because of complex 3-dimensional myocardial and vascular geometry. We characterized electrophysiological alterations a simpler 2-dimensional geometry cultured neonatal rat ventricular myocyte monolayers. Methods Results— Optical mapping intracellular Ca (Ca i ) voltage was performed with the use Rhod 2-AM Rh-237, respectively. Regional...
Melanoma has an extremely poor prognosis due to its rapidly progressive and highly metastatic nature. Several therapeutic drugs have recently become available, but are effective only against melanoma with specific BRAF gene mutation. Thus, there is a need identify other target molecules. We show here that Transient receptor potential, canonical 3 (TRPC3) widely expressed in human melanoma. found pharmacological inhibition of TRPC3 pyrazole compound, Pyr3, decreased cell proliferation...
Repolarization alternans is a harbinger of sudden cardiac death, particularly when it becomes spatially discordant. Alternans, beat-to-beat alternation in the action potential duration (APD) and intracellular Ca (Cai), can arise from either tissue heterogeneities or dynamic factors. Distinguishing between these mechanisms normal difficult because inherent complex three-dimensional heterogeneities. To evaluate repolarization simpler two-dimensional substrate, we optically recorded voltage...
1. In order to investigate the mechanism underlying MgATP-dependent recovery of ATP-sensitive potassium (KATP) channels, we expressed Kir6.2/SUR2A (inwardly rectifying K+ channel subunit/sulfonylurea receptor) or C-terminal-truncated Kir6.2 (Kir6.2DeltaC26) in COS7 cells (Green monkey kidney cells), and carried out inside-out patch clamp experiments. 2. After excision ATP-free internal solution, activity channels could be maximally recovered by application 5 mM MgATP. Subsequent 100 microM...
In the ATP‐dependent K + (K ATP ) channel pore‐forming protein Kir6.2, mutation of three positively charged residues, R50, K185 and R201, impairs ability to close channel. The mutations do not change open probability ( P o in absence ATP, supporting involvement these residues binding. We recently proposed that at least two interact with phosphate groups cause closure: β group interacts initiate closure, while α R201 stabilize channel's closed state. present study we replaced positive...
Mitochondria play key roles in the differentiation and maturation of human cardiomyocytes (CMs). As induced pluripotent stem cell-derived (hiPSC-CMs) hold potential treatment heart diseases, we sought to identify mitochondrial pathways regulators, which may provide targets for improving cardiac maturation. Proteomic analysis was performed on enriched protein extracts isolated from hiPSC-CMs differentiated dermal fibroblasts (dFCM) (cFCM) at time points between 12 115 days differentiation,...
We recently characterized two distinct mechanisms by which the polyamine spermine blocks Kir2.1 channels: (1) reduction of negative surface charges in cytoplasmicpore, thereby reducing single‐channel conductance, and (2) direct open channel transmembrane pore block. The extent to charge component is mediated passive screening versus binding polyamines these charges, as well block are synergistic, simply additive, was not established. To address issues, macroscopic currents were recorded from...