Gil Bub

Gil Bub
McGill University | McGill · Department of Physiology

About

120
Publications
12,511
Reads
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1,855
Citations
Citations since 2017
48 Research Items
1028 Citations
2017201820192020202120222023050100150200250
2017201820192020202120222023050100150200250
2017201820192020202120222023050100150200250
2017201820192020202120222023050100150200250
Additional affiliations
August 2016 - present
McGill University
Position
  • Professor (Associate)
January 2006 - August 2016
University of Oxford
Position
  • Lecturer

Publications

Publications (120)
Article
Full-text available
In an excitable medium, a stimulus generates a wave that propagates in space until it reaches the boundary or collides with another wave and annihilates. We study the dynamics generated by two periodic sources with different frequencies in excitable cardiac tissue culture using optogenetic techniques. The observed rhythms, which can be modeled usin...
Article
Full-text available
Cardiac action potential (AP) shape and propagation are regulated by several key dynamic factors such as ion channel recovery and intracellular Ca²⁺ cycling. Experimental methods for manipulating AP electrical dynamics commonly use ion channel inhibitors that lack spatial and temporal specificity. In this work, we propose an approach based on optog...
Preprint
Full-text available
Coupled electro-mechanical waves define heart’s function in health and disease. Genetic abnormalities, drug-triggered or acquired pathologies can disrupt and uncouple these waves with potentially lethal consequences. Optical mapping of electrical waves using fluorescent dyes or genetically-encoded sensors in human induced pluripotent stem cell deri...
Article
Funding Acknowledgements Type of funding sources: None. Cardiac action potential (AP) shape and propagation are regulated by several key dynamic factors such as ions channel recovery and intracellular Ca2+-cycling. Experimental methods for manipulating AP electrical dynamics commonly use ion channel inhibitors that lack spatial and temporal specifi...
Article
Full-text available
Fast volumetric imaging is essential for understanding the function of excitable tissues such as those found in the brain and heart. Measuring cardiac voltage transients in tissue volumes is challenging, especially at the high spatial and temporal resolutions needed to give insight to cardiac function. We introduce a new imaging modality based on s...
Article
Full-text available
Optical techniques for recording and manipulating cellular electrophysiology have advanced rapidly in just a few decades. These developments allow for the analysis of cardiac cellular dynamics at multiple scales while largely overcoming the drawbacks associated with the use of electrodes. The recent advent of optogenetics opens up new possibilities...
Article
Full-text available
Optical mapping is widely used in experimental cardiology, as it allows visualization of cardiac membrane potential and calcium transients. However, optical mapping measurements from a single heart or cell culture can produce several gigabytes of data, warranting automated computer analysis. Here we present COSMAS, a software toolkit for automated...
Article
Full-text available
The development of new approaches to control cardiac arrhythmias requires a deep understanding of spiral wave dynamics. Optogenetics offers new possibilities for this. Preliminary experiments show that sub-threshold illumination affects electrical wave propagation in the mouse heart. However, a systematic exploration of these effects is technically...
Article
Full-text available
Aims Gp91-containing NADPH oxidases (NOX2) are a significant source of myocardial superoxide production. An increase in NOX2 activity accompanies atrial fibrillation (AF) induction and electrical remodelling in animal models and predicts incident AF in humans; however, a direct causal role for NOX2 in AF has not been demonstrated. Accordingly, we i...
Article
Full-text available
We introduce a random access parallel (RAP) imaging modality that uses a novel design inspired by a Newtonian telescope to image multiple spatially separated samples without moving parts or robotics. This scheme enables near simultaneous image capture of multiple petri dishes and random-access imaging with sub-millisecond switching times at the ful...
Article
Cardiac action potential (AP) shape and propagation are regulated by several key dynamic factors such as ion channel recovery and intracellular Ca2+ cycling. Experimental methods for manipulating AP electrical dynamics commonly use ion channel inhibitors that lack spatial and temporal specificity. In this work, we propose an approach based on optog...
Article
Excitable media sustain circulating waves. In the heart, sustained circulating waves can lead to serious impairment or even death. To investigate factors affecting the stability of such waves, we have used optogenetic techniques to stimulate a region at the apex of a mouse heart at a fixed delay after the detection of excitation at the base of the...
Preprint
Full-text available
Fast volumetric imaging is essential for understanding the function of excitable tissues such as those found in the brain and heart. Measuring cardiac voltage transients in tissue volumes with spatial and temporal resolutions needed to give insight to cardiac function has so far been impossible. We introduce a new imaging modality based on simultan...
Article
Full-text available
Cardiac stimulation via sympathetic neurons can potentially trigger arrhythmias. We present approaches to study neuron-cardiomyocyte interactions involving optogenetic selective probing and all-optical electrophysiology to measure activity in an automated fashion. Here we demonstrate the utility of optical interrogation of sympathetic neurons and t...
Article
Full-text available
Interactions along the neuro-cardiac axis are being explored with regard to their involvement in cardiac diseases, including catecholaminergic polymorphic ventricular tachycardia, hypertension, atrial fibrillation, long QT syndrome and sudden death in epilepsy. Interrogation of the pathophysiology and pathogenesis of neuro-cardiac diseases in anima...
Preprint
Full-text available
Alterations in autonomic function are known to occur in cardiac conditions including sudden cardiac death. Cardiac stimulation via sympathetic neurons can potentially trigger arrhythmias. Dissecting direct neural-cardiac interactions at the cellular level is technically challenging and understudied due to the lack of experimental model systems and...
Article
Full-text available
A monolayer of chick embryo cardiac cells grown in an annular geometry supports two simultaneous reentrant excitation waves that circulate as a doublet. We propose a mechanism that can lead to such behavior. The velocity restitution gives the instantaneous velocity of a wave as a function of the time since the passage of the previous wave at a give...
Article
Full-text available
Background: Following myocardial infarction (MI), the myocardium is prone to calcium-driven alternans, which typically precedes ventricular tachycardia and fibrillation. MI is also associated with remodeling of the sympathetic innervation in the infarct border zone, although how this influences arrhythmogenesis is controversial. We hypothesize that...
Article
Full-text available
Optogenetics is an emerging method that uses light to manipulate electrical activity in excitable cells exploiting the interaction between light and light-sensitive depolarizing ion channels, such as channelrhodopsin-2 (ChR2). Initially used in the neuroscience, it has been adopted in cardiac research where the expression of ChR2 in cardiac prepara...
Data
Figure S1. Cross‐talk free optogenetic stimulation during VSD imaging. Figure S2. Dose‐response curves to different ChR2 stimulation patterns designed as reported by the blue ROIs on the fluorescence image of the heart. Figure S3. VSD signal‐to‐noise ratio and threshold selection. Figure S4. Optical manipulation of atrioventricular delay.
Article
Full-text available
Background: Cardiac alternans is an important precursor to arrhythmia, facilitating formation of conduction block, and re-entry. Diseased hearts were observed to be particularly vulnerable to alternans, mainly in heart failure or after myocardial infarction. Alternans is typically linked to oscillation of calcium cycling, particularly in the sarcop...
Article
Full-text available
Key points: Although optogenetics has clearly demonstrated the feasibility of cardiac manipulation, current optical stimulation strategies lack the capability to react acutely to ongoing cardiac wave dynamics. Here, we developed an all-optical platform to monitor and control electrical activity in real-time. The methodology was applied to restore...
Article
Full-text available
Synaptic plasticity is defined as the ability of synapses to change their strength of transmission. Plasticity of synaptic connections in the brain is a major focus of neuroscience research, as it is the primary mechanism underpinning learning and memory. Beyond the brain however, plasticity in peripheral neurons is less well understood, particular...
Article
Full-text available
Caveolae are signal transduction centers, yet their subcellular distribution and preservation in cardiac myocytes after cell isolation are not well documented. Here, we quantify caveolae located within 100 nm of the outer cell surface membrane in rabbit single-ventricular cardiomyocytes over 8 h post-isolation and relate this to the presence of cav...
Article
Atrial fibrillation, NADPH oxidases, ryanodine receptor Background Gp91-containing NADPH oxidases (NOX2) are a significant source of reactive oxygen species (ROS) in the human atrial myocardium. An increase in NOX2 activity accompanies atrial fibrillation (AF) induction and electrical remodelling in animal models and predicts incident AF in humans...
Article
Full-text available
The border zone (BZ) of the viable myocardium adjacent to an infarct undergoes extensive autonomic and electrical remodeling and is prone to repolarization alternans-induced cardiac arrhythmias. BZ remodeling processes may promote or inhibit Ca²⁺ and/or repolarization alternans and may differentially affect ventricular arrhythmogenesis. Here, we us...
Article
Full-text available
Hypertension induces considerable cardiac remodelling, such as hypertrophy, interstitial fibrosis, and abnormal activity of cardiac sympathetic nervous system, which are established risk factors in several highly dangerous heart diseases, such as ventricular fibrillation and congestive heart failure. All these risk factors and heart diseases are st...
Article
Full-text available
In the present study, channelrhodopsin 2 (ChR2) was specifically introduced into murine cells expressing the Phenylethanolamine n-methyltransferase (Pnmt) gene, which encodes for the enzyme responsible for conversion of noradrenaline to adrenaline. The new murine model enabled the identification of a distinctive class of Pnmt-expressing neuroendocr...
Article
Full-text available
Cardiac arrhythmias are one of the most frequent causes of death worldwide. A popular biological model used to study arrhythmogenesis is the cultured cardiac cell monolayer, which provides a good trade-off between physiological relevance and experimental access. Excitation wave patterns are imaged using high-bandwidth detectors, producing large dat...
Article
Both biomedical research and clinical practice rely on complex datasets for the physiological and genetic characterization of human hearts in health and disease. Given the complexity and variety of approaches and recordings, there is now growing recognition of the need to embed computational methods in cardiovascular medicine and science for analys...
Article
Full-text available
Cardiac tissue is an excitable system that can support complex spatiotemporal dynamics, including instabilities (arrhythmias) with lethal consequences. While over the last two decades optical mapping of excitation (voltage and calcium dynamics) has facilitated the detailed characterization of such arrhythmia events, until recently, no precise tools...
Article
Full-text available
Aims: Implantable cardiac vagal nerve stimulators are a promising treatment for ventricular arrhythmia in patients with heart failure. Animal studies suggest the antifibrillatory effect may be nitric oxide (NO) dependent, although the exact site of action is controversial. We investigated whether a stable analogue of acetylcholine could raise vent...
Article
Full-text available
Both biomedical research and clinical practice rely on complex datasets for the physiological and genetic characterization of human hearts in health and disease. Given the complexity and variety of approaches and recordings, there is now growing recognition of the need to embed computational methods in cardiovascular medicine and science for analys...
Article
Full-text available
In nature, macroscopic excitation waves1, 2 are found in a diverse range of settings including chemical reactions, metal rust, yeast, amoeba and the heart and brain. In the case of living biological tissue, the spatiotemporal patterns formed by these excitation waves are different in healthy and diseased states2, 3. Current electrical and pharmacol...
Article
Full-text available
In nature, excitable reaction-diffusion systems found in diverse settings (e.g. chemical reactions, metal rust, yeast, amoeba, heart, brain) generate geometrically similar macroscopic waves(1,2). For the heart and brain, the spatiotemporal patterns formed by these excitation waves separate healthy from diseased states(1-3). Current electrical and p...
Article
In cardiac imaging, the spacing between sub-cellular sarcomere structures is of great importance to physiologists in understanding muscle design and performance. Making accurate measurements of the sarcomere length (SL) presents a significant imaging challenge owing to the size of the SL (∼2μm) and its naturally low variability (<6%), requiring a h...
Article
Full-text available
Bradycardic agents are of interest for the treatment of ischemic heart disease and heart failure, as heart rate (HR) is an important determinant of myocardial oxygen consumption. To investigate the propensity of hydroxychloroquine (HCQ) to cause bradycardia. We assessed the effects of HCQ: i) on cardiac beating rate in vitro (mice); ii) on the If c...
Article
Remote focussing microscopy offers many advantages when acquiring volumetric data from living tissue. The all-optical means of refocussing does not agitate the specimen by moving either the stage or imaging objective. Aberrationcompensated imaging extends over volumes as large as 450 μm x 450 μm x 200 μm (X, Y and Z) allowing data to be collected f...
Article
In cardiac imaging, the spacing between sub-cellular sarcomere structures is of great importance to physiologists in understanding muscle design and performance. Making accurate measurements of the sarcomere length (SL) presents a significant imaging challenge owing to the size of the SL (~2μm) and its naturally low variability (<6%), requiring a h...
Article
Full-text available
A fast scanning light-sheet microscope that produces multicolour, dynamic images of living tissue could provide fresh insights into the brain's neural circuits.
Article
Full-text available
The autonomic nervous system plays an important role in the modulation of normal cardiac rhythm, but is also implicated in modulating the hearts susceptibility to re-entrant ventricular and atrial arrhythmias. The mechanisms by which the autonomic nervous system is pro-arrhythmic or anti-arrhythmic is multifaceted and varies for different types of...
Article
Introduction: Beta-blockers (BB) are the only anti-arrhythmic drugs that improve mortality in patients with ischaemic heart disease, but a significant risk of arrhythmia remains. During high-level sympathetic drive, such as during myocardial infarction, co-transmitters including neuropeptide Y (NPY) can be released with norepinephrine. NPY is a pot...
Article
Full-text available
Remote focussing microscopy allows sharp, in-focus images to be acquired at high speed from outside of the focal plane of an objective lens without any agitation of the specimen. However, without careful optical alignment, the advantages of remote focussing microscopy could be compromised by the introduction of depth-dependent scaling artifacts. To...
Conference Paper
A variety of arrhythmias have been attributed to formation of large scale patterns of excitation such as formation and break-up of spiral waves. We investigate the relationship between neuronal activity and evolution of macroscopic spatiotemporal dynamics. We also aim to understand the role of target-derived trophic nerve growth factors (NGF) on th...
Article
Although application of a 9V battery to the epicardial surface is a simple method of ventricular fibrillation induction, the fundamental mechanisms underlying this process remain unstudied. We used a combined experimental and modelling approach to understand how the interaction of direct current (DC) from a battery may induce reentrant activity wit...