A5089811873- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Neuroscience and Neural Engineering
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Pluripotent Stem Cells Research
- Neural dynamics and brain function
- Cardiomyopathy and Myosin Studies
- Autism Spectrum Disorder Research
- Electrostatic Discharge in Electronics
- stochastic dynamics and bifurcation
- CRISPR and Genetic Engineering
- Mitochondrial Function and Pathology
- Hypothalamic control of reproductive hormones
- Photoreceptor and optogenetics research
- Nicotinic Acetylcholine Receptors Study
- Genomic variations and chromosomal abnormalities
- Semiconductor materials and devices
- Ion Transport and Channel Regulation
- Prenatal Screening and Diagnostics
- Muscle Physiology and Disorders
- Computational Drug Discovery Methods
- Pregnancy-related medical research
- Congenital heart defects research
- Signaling Pathways in Disease
University at Buffalo, State University of New York
2015-2024
Jacobs (United States)
2024
New York University
2010-2022
Jacobs Institute
2018-2019
Buffalo State University
2004-2018
Buffalo Medical Group
2009-2016
Albany State University
2012-2014
University at Albany, State University of New York
2012-2014
Institute of Molecular Biology and Biophysics
2011-2013
Beijing Obstetrics and Gynecology Hospital
2011-2013
We have developed a mathematical model of the mouse ventricular myocyte action potential (AP) from voltage-clamp data underlying currents and Ca2+ transients. Wherever possible, we used Markov models to represent molecular structure function ion channels. The includes detailed intracellular dynamics, with simulations localized events such as sarcoplasmic release into small volume bounded by sarcolemma reticulum. Transporter-mediated fluxes bulk cytosol are closely matched experimentally...
Autism and autism spectrum disorder (ASD) typically arise from a mixture of environmental influences multiple genetic alterations. In some rare cases, such as Timothy syndrome (TS), specific mutation in single gene can be sufficient to generate or ASD most patients, potentially offering insights into the etiology general. Both variants TS (the milder TS1 more severe TS2) missense mutations alternatively spliced exons that cause same G406R replacement Ca V 1.2 L-type calcium channel. We...
Familial hypertrophic cardiomyopathy (HCM) is one the most common heart disorders, with gene mutations in cardiac sarcomere. Studying HCM patient-specific induced pluripotent stem-cell (iPSC)-derived cardiomyocytes (CMs) would benefit understanding of mechanism, as well development personalized therapeutic strategies.To investigate molecular mechanism underlying abnormal CM functions HCM, we derived iPSCs from an patient a single missense mutation (Arginine442Glycine) MYH7 gene. CMs were...
Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene (DMD), and characterized progressive weakness skeletal cardiac muscles. Currently, dilated cardiomyopathy due to muscle loss one of major causes lethality late-stage DMD patients. To study molecular mechanisms underlying heart, we generated cardiomyocytes (CMs) from healthy control induced pluripotent stem cells (iPSCs). iPSC-derived CMs (iPSC-CMs) displayed deficiency, as well elevated levels resting Ca(2+),...
Rationale: Atrial fibrillation (AF) contributes significantly to morbidity and mortality in elderly hypertensive patients has been correlated enhanced atrial fibrosis. Despite a lack of direct evidence that fibrosis causes AF, reversal is considered plausible therapy. Objective: To evaluate the efficacy antifibrotic hormone relaxin (RLX) suppressing AF spontaneously rats (SHR). Methods Results: Normotensive Wistar-Kyoto (WKY) SHR were treated for 2 weeks with vehicle (WKY+V SHR+V) or RLX...
Mechanoelectric transduction can initiate cardiac arrhythmias. To examine the origins of this effect at cellular level, we made whole cell voltage-clamp recordings from acutely isolated rat ventricular myocytes under controlled strain. Longitudinal stretch elicited noninactivating inward cationic currents that increased action potential duration. These stretch-activated could be blocked by 100 μM Gd 3+ but not octanol. The current-voltage relationship was nearly linear, with a reversal...
Key points Tymothy syndrome (TS) is a multisystem disorder featuring cardiac arrhythmias, autism and adrenal gland dysfunction that originates from de novo point mutation in the gene encoding Cav1.2 ( CACNA1C ) L‐type channel. To study role of channel signals autism, autistic TS2‐neo mouse has been generated bearing G406R point‐mutation associated with TS type‐2. Using heterozygous mice, we report reduces rate inactivation shifts leftward activation channels, causing marked increase resting...
The purpose of this investigation was to determine what extent the swelling-activated Cl- current (ICl,swell) contributes swelling-induced changes in resting membrane potential and action duration (APD) ventricular myocytes. Action potentials were recorded from guinea pig myocytes using conventional whole cell recording techniques. Cell swelling caused initial lengthening followed by a variable shortening APD. In 59% cells secondary APD had 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid...
Women have a higher risk of lethal arrhythmias than men in long QT syndrome type 2 (LQTS2), but the mechanisms remain uncertain due to limited availability healthy control human tissue. We previously reported that female rabbits, estrogen increases arrhythmia drug-induced LQTS2 by upregulating L-type Ca2+ (ICa,L) and sodium-calcium exchange (INCX) currents at base epicardium genomic mechanism. This study investigates if effects on rabbit ICa,L INCX apply hearts. Postmortem left ventricular...
Timothy Syndrome (TS) arises from a point mutation in the human voltage-gated L-type Ca2+ channel (Cav1.2). TS is associated with cardiac arrhythmias and sudden death, as well congenital heart disease, impaired cognitive function, autism spectrum disorders. results de novo gain-of-function which affects voltage dependent component of Cav1.2 inactivation. We created knock-in mouse. No homozygous mice survived, but heterozygous TS2-NEO (with neocassette situ) had normal outward appearance...
Abstract Brugada syndrome (BrS) is an inherited cardiac arrhythmia commonly associated with SCN5A mutations, yet its ionic mechanisms remain unclear due to a lack of cellular models. Here, we used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from BrS patient (BrS1) evaluate the roles Na + currents ( I ) and transient outward K in action potential (AP) changes. To understand role these current changes repolarization employed dynamic clamp “electronically express” K1...
KCNQ1 (Kv7.1 or KvLQT1) encodes the alpha‐subunit of a voltage‐gated potassium channel found in tissues including heart, brain, epithelia and smooth muscle. Tissue‐specific characteristics current are diverse, due to modification by ancillary subunits. In associates with KCNE1 (MinK), producing slowly activating voltage‐dependent channel. epithelia, co‐assembles KCNE3 (Mirp2) constitutively open Chromanol 293B is selective blocker. We studied drug binding frequency dependence on subunits...
Abstract To study the role of L‐type voltage‐gated Ca ++ channels in oligodendrocyte development, we used a mouse model Timothy syndrome (TS) which gain‐of‐function mutation α1 subunit channel Cav1.2 gives rise to an autism spectrum disorder (ASD). Oligodendrocyte progenitor cells (OPCs) isolated from cortex TS mice showed greater influx and displayed characteristics suggestive advanced maturation compared control OPCs, including more complex morphology higher levels myelin protein...
The congenital short QT syndrome (SQTS) is a cardiac condition that leads to abbreviated ventricular repolarization and an increased susceptibility arrhythmia sudden death. SQT3 form of the due mutations KCNJ2 gene encodes Kir2.1, critical component channels underlying inwardly rectifying K+ current, IK1. first reported mutation gives rise D172N Kir2.1 mutation, consequences which have been studied on recombinant in vitro cell tissue simulations. aim this study was establish effects through...