An important goal of the Cardiac Bioelectricity and Arrhythmia Center (CBAC), Washington University in St. Louis is to enhance and promote education and training in biomedical engineering, life sciences, and clinical medicine. The CBAC hosts seminars each semester, where world renowned clinicians and researchers are invited to lecture. These seminars are attended by engineering, physics and medical school faculty and graduate students, as well as professionals from outside the university. These seminar videos are open to the general public.
Disclaimer: All material within each video file was filmed during a Cardiac Bioelectricity and Arrhythmia Center (CBAC) seminar at Washington University in St. Louis. It was made available on this website with permission from the speaker, who reserves and holds all rights. The video files are for educational purposes only and may not be reproduced, distributed or copied in any format.
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For more information about the seminars, please contact Huyen (Gwen) Nguyen at firstname.lastname@example.org
Lucie Delemotte Ph.D.
Voltage-gated ion channels are the membrane proteins whose opening and closing are responsible for the propagation of action potential in excitable cells. Their dysfunction leads to diseases such as cardiac arrhythmias, epilepsy or muscle ataxia. As such, they constitute major drug targets.
Voltage-sensitive ion channels function depends in a large part on their structure, and high-resolution structures of prototype channels have been known since the early 2000s. Nevertheless, we still lack a detailed understanding of their dynamic behavior as well as the structural ensemble that make up their functional cycle. Both of these aspects are critical for designing innovative and ...Read More
Eleonora Grandi Ph.D.
Nathan Huebsch Ph.D.
Joseph C. Wu M.D., Ph.D.
Richard W. Aldrich Ph.D.
Penelope A. Boyden Ph.D
Alfred E. Buxton M.D.
David J. Callans M.D., F.H.R.S.
David Fedida B.M., B.Ch., Ph.D.
Alan Garfinkel Ph.D
Mathematical models of cardiac arrhythmias come in two distinct forms. High-dimensional, biophysically detailed models give us realism; they talk about biophysical quantities that can be experimentally and clinically altered.
But there is another critical kind of modeling: Low-dimensional modeling tries to isolate the essential dynamical phenomena responsible for a qualitative outcome. It gives us deeper insights into causal mechanisms. The most important technique of low-dimensional modeling is bifurcation theory. A bifurcation is a qualitative change in the solution to a differential equation, as a key parameter is varied. Identification of these key parameters then becomes the central task, because it ...Read More
Michael Glikson M.D.
Andrew R. Marks M.D.
Ryanodine receptor (RyR) channels are required for release of calcium from intracellular stores, aprocess essential for many cellular functions including excitation-contraction (EC) coupling in skeletal and cardiac muscle, and hormone and neurotransmitter release. They are the largest ion channels, comprised of the four identical -565 kDa channel-forming protomers, as well as regulatory subunits, enzymes and their respective targeting/anchoring proteins, in a macromolecular complex that exceeds three million daltons. We have obtained high-resolution cryo-electron microscopy (Cryo-EM) reconstructions from highly purified rabbit skeletal muscle RyR1 in the open and closed states. Our data reveal that RyRs are members of the six transmembrane ...Read More
Riccardo Olcese Ph.D.
Advancements in Implantable Cardioverter Defibrillator Therapy: Focus on Lead Technology and Defibrillation
Andrea M. Russo M.D., F.A.C.C., F.H.R.S.
Patrick T. Elinor M.D., Ph.D
Atrial fibrillation (AF) affects over 3 million individuals in the US and 4.5 million individuals in Europe. In addition, AF is associated with an increased risk of stroke, dementia, heart failure, death and health care costs. Many AF risk factors have been identified including aging, cardiovascular disease, and family history. Although heritable forms of AF were previously considered rare, we have established evidence of substantial AF heritability over the last decade. Genome-wide association studies (GWAS) provide a powerful tool to identify common variants underlying disease risk. In 2007 a GWAS for AF identified a locus on chromosome 4q25. Later that ...Read More
Emilia Entcheva Ph.D.
Optical targeting (stimulation or recording) allows distributed parallel access to thousands and even millions of cells and locations at the same time, and within the tissue setting; optical targeting is high-throughput by nature. In this talk, I will discuss and demonstrate the combination of optogenetic stimulation with optical imaging of electrical activity in cardiomyocytes, i.e. the realization of “all-optical electrophysiology” in a high-throughput manner (HTS). Examples will include demonstration of cardiac “wave steering” by light and the use of a new fully-automated all-optical HTS platform (OptoDyCE) for drug screening using patient-derived cardiomyocytes (iPS-CMs).
Glenn I. Fishman M.D., F.A.C.C., F.A.H.A., F.A.C.P., F.H.R.S
Our laboratory has been interested in multiple facets of cardiac electrophysiology and arrhythmia mechanisms, with a particular focus on identifying novel regulators of cardiac excitability, impulse propagation, and arrhythmia susceptibility. Our most recent studies seek to decipher the mechanisms responsible for specification, maturation and function of the specialized cardiac conduction system and identifying novel transcriptional regulators that influence cardiomyocyte electrophysiological diversity and integrated cardiac excitability. I will describe the role of two novel transcription factors (one recently reported and the second still a work in progress) that appear to play critical roles in establishing functional diversity throughout individual compartments of ...Read More
Richard W. Gross M.D., Ph.D
Francis E. Marchlinski M.D.
Andrew D. McCulloch Ph.D.
Mechanical stretch of cardiac muscle affects myocyte electrophysiology is potentially arrhythmogenic. We investigated the effects of stretch in vitro and in the intact heart on action potential conduction. Using optical mapping to measure in isolated mouse hearts and in micropatterned mouse cardiomyocyte we found that conduction velocity decreased rapidly and reversibly with volume loading and stretch. This slowing was not altered by stretch-activated channel inhibition, but was abrogated when caveolae were disrupted by genetic deletion of caveolin-3 or chemical depletion of membrane cholesterol. Electron microscopy showed that stretch in wild-type mouse hearts, causes recruitment of caveolae to the sarcolemma. Stretch ...Read More
Peter J. Mohler Ph.D.
Our research is focused on the mechanisms underlying the targeting and regulation of membrane-associated (ion channels, transporters, receptors) and signaling proteins in cardiac and other excitable cells. In particular, we are interested in the role of membrane-associated ankyrin and spectrin family of polypeptides in the targeting and function of ion channels and transporters as well as kinases and phosphatases. A primary focus of the lab is the role of the ankyrin-G-based pathway for targeting voltage gated sodium channels to the intercalated disc of cardiomyocytes. We have discovered a direct requirement of ankyrin-G for Na channel targeting and have linked human ...Read More
Saman Nazarian M.D., Ph.D.
Amit Noheria M.B.B.S. (M.D.), S.M.
Blanca Rodriguez Ph.D.
Longer Lasting Torsade de Pointes Arrhythmias Require Reentry for its Maintenance in the CAVB Dog Model
Marc A. Vos Ph.D.
The mechanism of Torsade de Pointes arrhythmias (TdP) has been under debate for many years. Focal activity as well as reentry have both been mentioned in the intiation as perpetuation of TdP. Therefore, the arrhythmogenic mechanisms responsible for TdP were once more investigated in the CAVB dog model, known for its high susceptibility for TdP. In five TdP-sensitive CAVB dogs, 56 needle electrodes were evenly distributed transmurally to record 240 unipolar local electrograms simultaneously. Nonterminating (NT) episodes were defibrillated after 10s. Software was developed to automatically detect activation times and to create 3D visualisations of the arrhythmia. For each episode ...Read More