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
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).
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
Geoffrey W. Abbott Ph.D.
Coronary Artery Disease (CAD) leads to more deaths in the U.S. and globally each year than any other single cause of death. An estimated half of CAD cases involve genetic predisposition; reduction of other risk factors can reduce CAD mortality and morbidity by >30%. The major challenge now is to develop more comprehensive prevention and treatment strategies for both genetic and environmental risk factors, necessitating a better mechanistic understanding of CAD. Another form of fatal heart disorder, Sudden Cardiac Death (SCD), accounts for ~1000 deaths per day in the U.S. SCD is thought to require an electric substrate, an ischemic ...Read More
Hugues Abriel M.D., Ph.D.
The field of molecular arrhythmology has progressed at an impressive pace during the past 20 years. Throughout the years, we have learned more and more about the genetic factors and molecular mechanisms underlying electrical abnormalities of the heart such as congenital long QT syndrome (LQTS) and Brugada syndrome. Since in most cases, the genes that are found to be mutated are encoding either the pore-forming subunit of cardiac ion channels or of ion channel regulatory proteins, the term “genetic cardiac channelopathies” has been used to define these disorders. Among the still-growing list of genes that lead to genetic cardiac channelopathies, ...Read More
Peter H. Backx Ph.D., D.V.M.
Regulation of Cardiac Calcium Channels in the Fight-or-Flight Response: From Molecular Mechanisms to Heart Failure
William Catterall Ph.D.
Intracellular calcium transients generated by activation of voltage-gated calcium (CaV) channels generate local signals, which initiate physiological processes such as secretion, synaptic transmission, and excitation-contraction coupling. Regulation of calcium entry through CaV channels is crucial for control of these physiological processes. In this article, I review experimental results that have emerged over several years showing that cardiac CaV1.2 channels form a local signaling complex, in which their proteolytically processed distal C-terminal domain, an A-Kinase Anchoring Protein, and cyclic AMP-dependent protein kinase (PKA) interact directly with the transmembrane core of the ion channel through the proximal C-terminal domain. This signaling complex ...Read More
Phillip S. Cuculich M.D. and Clifford G. Robinson M.D.
Donald Hilgemann Ph.D.
TingTing Hong M.D.; Ph.D.
The Hong Lab has cloned the cardiac isoform of the membrane deformation protein BIN1, which we refer to as cBIN1. The story of cBIN1 originated as a protein trafficking finding, identifying how calcium channels are delivered to T-tubule membrane. In subsequent studies, they have found that cBIN1 forms membrane microdomains in T-tubule membrane, affecting calcium transients, dyad organization, and membrane excitability. In heart failure, cBIN1 is reduced. cBIN1 is also turned over into blood from viable cardiomyocytes. In clinical studies, they are finding that cBIN1 provides a window into the metabolic health of heart muscle and may help in clinical decision making.
João A.C. Lima M.D.
Vivek Reddy M.D.
Scorpions, Snakes, Insecticides and Coffee: Insights into the Genesis of Calcium-Dependent Arrhythmias
Héctor H. Valdivia M.D., Ph.D.
Quantitative T-wave Alternans Analysis for Sudden Cardiac Death Risk Assessment and Guiding Therapy: Answered and Unanswered Questions
Richard L. Verrier Ph.D., F.A.C.C., F.H.R.S.
Identification of individuals at risk for sudden cardiac death (SCD), the main cause of adult mortality in developed countries, remains a major challenge. The scope of this public health problem is sizeable, as one million SCDs occur annually worldwide. In 30% to 40% of cases, death is the first indication of underlying heart disease. The main contemporary noninvasive marker, left ventricular ejection fraction (LVEF), has not proved adequately reliable, as the majority of individuals who die suddenly have relatively preserved cardiac mechanical function. Monitoring of T-wave alternans (TWA), a beat-to-beat fluctuation in ST-segment or T-wave morphology, on ambulatory electrocardiogram ECG ...Read More
Paul J. Wang M.D.
Mark Anderson M.D., Ph.D.
C. William Balke M.D., F.A.C.P., F.A.H.A.
Connie R. Bezzina Ph.D.
The Tangling of Three Dynamical Systems in the Heart: Interactions of the Electrical, the Ca2+ Signaling, and the Contractile Systems
Ye Chen-Izu M.S. Ph.D.
Cardiac excitation-contraction is controlled by three dynamic systems – the electrical system, the Ca2+ signaling system, and the contractile system. In the classic paradigm, electrical excitation controls Ca2+ signaling which, in turn, controls muscle contraction. Early work focused on investigating each dynamic system in isolation. However, recent studies show that defects in the contractile system can feedback to disrupt Ca2+ signaling system and cause electrical arrhythmias. We have developed innovative techniques and new methods to study the interaction of these dynamic systems. (1) The action potential (AP)-clamp sequential dissection method enables recording of multiple ionic currents under AP-clamp in the ...Read More
Sándor Györke Ph.D.
G Protein Coupled Receptors, Phosphoinositide Lipids, and Ion Channels Control Membrane Excitability
Bertil Hille Ph.D.
Ion channel function and electrical excitability are modulated by hormones and neurotransmitters acting on G-protein coupled receptors. Intracellular cyclic nucleotides and calcium are common intermediaries after receptor activation. We found two others: first, fast release of Gβγ subunits from G proteins and second, a slower depletion of the plasma membrane phosphoinositide lipid PI(4,5)P2. This lipid is a cofactor for many plasma membrane ion channels. As biophysicists, we have studied and modeled the dynamics of G-protein signaling. The lipid connection made us interested in the pools of cellular phosphoinositides, their location, their perturbation by receptors, subcellular trafficking, and actions. All these ...Read More