Overview

Although the neonate heart is completely responsible for delivering blood to the body, it is still immature in many respects. This is particularly true of the cardiac contractile system and its regulatory mechanisms. The strength of cardiac contraction is determined by the amount of calcium (Ca2+) delivered to the contractile element. Thus the levels of Ca2+ inside each cell (or cardiomyocyte) rise and fall each beat, and peak value can vary substantially in response to physiological needs and/or hormones such as adrenaline. How this is achieved in the neonate heart, although poorly understood, is quite different from the adult heart. This has clinical implications; for example, in children with congenital heart disease (present in 1% of live births), the heart must often be arrested during surgical correction. However, these techniques are largely derived from our understanding of the adult heart. We hope to improve the success rate of surgical correction, and better understand “normal” heart development and the deviations that occur in congenital heart diseases.

Publications

In vivo characterization of doxycycline-mediated protection of aortic function and structure in a mouse model of Marfan syndrome-associated aortic aneurysm
Scientific Reports
Jason Z. Cui and Ling Lee and Xiaoye Sheng and Fanny Chu and Christine P. Gibson and Taline Aydinian and David C. Walker and George G. S. Sandor and Pascal Bernatchez and Glen F. Tibbits and Cornelis van Breemen and Mitra Esfandiarei
DOI: 10.1038/s41598-018-38235-6
12/2019

Modeling Atrial Fibrillation using Human Embryonic Stem Cell-Derived Atrial Tissue
Scientific Reports
Zachary Laksman and Marianne Wauchop and Eric Lin and Stephanie Protze and Jeehoon Lee and Wallace Yang and Farzad Izaddoustdar and Sanam Shafaattalab and Lior Gepstein and Glen F. Tibbits and Gordon Keller and Peter H. Backx
DOI: 10.1038/s41598-017-05652-y
12/2017

Changes in the dynamics of the cardiac troponin C molecule explain the effects of Ca2+-sensitizing mutations
Journal of Biological Chemistry
Charles M. Stevens and Kaveh Rayani and Gurpreet Singh and Bairam Lotfalisalmasi and D. Peter Tieleman and Glen F. Tibbits
DOI: 10.1074/jbc.M116.770776
07/2017

Erratum: Functional Assessment of Cardiac Responses of Adult Zebrafish (Danio rerio) to Acute and Chronic Temperature Change Using High-Resolution Echocardiography (PLoS ONE (2016) 11:1 (e0145163) DOI: 10.1371/journal.pone.0145163)
PLoS ONE
DOI: 10.1371/journal.pone.0149741
2016

Functional assessment of cardiac responses of adult zebrafish (danio rerio) to acute and chronic temperature change using high-resolution echocardiography
PLoS ONE
DOI: 10.1371/journal.pone.0145163
2016

Construction and use of a zebrafish heart voltage and calcium optical mapping system, with integrated electrocardiogram and programmable electrical stimulation
American journal of physiology. Regulatory, integrative and comparative physiology
DOI: 10.1152/ajpregu.00001.2015
2015

Construction and use of a zebrafish heart voltage and calcium optical mapping system, with integrated electrocardiogram and programmable electrical stimulation
American Journal of Physiology - Regulatory Integrative and Comparative Physiology
DOI: 10.1152/ajpregu.00001.2015.
2015

Automatic cycle averaging for denoising approximately periodic spatiotemporal signals
IEEE Transactions on Medical Imaging
DOI: 10.1109/TMI.2014.2323201
2014

Optical mapping of the electrical activity of isolated adult zebrafish hearts: Acute effects of temperature
American Journal of Physiology - Regulatory Integrative and Comparative Physiology
DOI: 10.1152/ajpregu.00002.2014
2014

Morphological phenotyping of mouse hearts using optical coherence tomography
Journal of Biomedical Optics
DOI: 10.1117/1.JBO.19.11.116007
2014

On identification of sinoatrial node in zebrafish heart based on functional time series from optical mapping
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference
DOI: 10.1109/EMBC.2013.6611048
2013

Adult teleost heart expresses two distinct troponin C paralogs: Cardiac TnC and a novel and teleost-specific ssTnC in a chamber- and temperature-dependent manner
Physiological Genomics
DOI: 10.1152/physiolgenomics.00074.2013
2013

The structure of cardiac troponin C regulatory domain with bound Cd 2+ reveals a closed conformation and unique ion coordination
Acta Crystallographica Section D: Biological Crystallography
DOI: 10.1107/S0907444913001182
2013

Familial hypertrophic cardiomyopathy related cardiac troponin C L29Q mutation alters length-dependent activation and functional effects of phosphomimetic troponin I
PLoS ONE
DOI: 10.1371/journal.pone.0079363
2013

Isolation and characterization of atrioventricular nodal cells from neonate rabbit heart
Circulation: Arrhythmia and Electrophysiology
DOI: 10.1161/CIRCEP.111.964056
2011

Colocalization of voltage-gated Na+ channels with the Na +/Ca2+ exchanger in rabbit cardiomyocytes during development
American Journal of Physiology - Heart and Circulatory Physiology
DOI: 10.1152/ajpheart.00798.2010
2011

Calcium handling in zebrafish ventricular myocytes
American Journal of Physiology - Regulatory Integrative and Comparative Physiology
DOI: 10.1152/ajpregu.00377.2010
2011

Crystal structure of cardiac troponin C regulatory domain in complex with cadmium and deoxycholic acid reveals novel conformation
Journal of Molecular Biology
DOI: 10.1016/j.jmb.2011.08.049
2011

Mechanistic basis for LQT1 caused by S3 mutations in the KCNQ1 subunit of iks
Journal of General Physiology
DOI: 10.1085/jgp.200910351
2010

Characterization of zebrafish (Danio rerio) NCX4: A novel NCX with distinct electrophysiological properties
American Journal of Physiology - Cell Physiology
DOI: 10.1152/ajpcell.00455.2008
2009

Distribution patterns of the Na+-Ca2+ exchanger and caveolin-3 in developing rabbit cardiomyocytes
Cell Calcium
DOI: 10.1016/j.ceca.2009.01.001
2009

Familial hypertrophic cardiomyopathy-related cardiac troponin C mutation L29Q affects Ca2+ binding and myofilament contractility
Physiological Genomics
DOI: 10.1152/physiolgenomics.00154.2007
2008

Gene structure evolution of the Na+-Ca2+ exchanger (NCX) family
BMC Evolutionary Biology
DOI: 10.1186/1471-2148-8-127
2008

Ontogeny of Ca2+-induced Ca2+ release in rabbit ventricular myocytes
American Journal of Physiology - Cell Physiology
DOI: 10.1152/ajpcell.00417.2007
2008

A KCNQ1 V205M missense mutation causes a high rate of long QT syndrome in a First Nations community of northern British Columbia: A community-based approach to understanding the impact
Genetics in Medicine
DOI: 10.1097/GIM.0b013e31817c6b19
2008

Hyperpolarization-activated cyclic nucleotide-modulated 'HCN' channels confer regular and faster rhythmicity to beating mouse embryonic stem cells
Journal of Physiology
DOI: 10.1113/jphysiol.2007.144329
2008

Functional and evolutionary relationships of troponin C
Physiological Genomics
DOI: 10.1152/physiolgenomics.00197.2007
2007

SR Ca2+ refilling upon depletion and SR Ca2+ uptake rates during development in rabbit ventricular myocytes
American Journal of Physiology - Cell Physiology
DOI: 10.1152/ajpcell.00241.2007
2007

Three-dimensional distribution of cardiac Na+-Ca2+ exchanger and ryanodine receptor during development
Biophysical Journal
DOI: 10.1529/biophysj.107.104943
2007

Real-time monitoring of intracellular calcium dynamic mobilization of a single cardiomyocyte in a microfluidic chip pertaining to drug discovery
Electrophoresis
DOI: 10.1002/elps.200700312
2007

L-type Ca2+ channel function and expression in neonatal rabbit ventricular myocytes
American Journal of Physiology - Heart and Circulatory Physiology
DOI: 10.1152/ajpheart.01093.2005
2006

Store-operated Ca2+ entry modulates sarcoplasmic reticulum Ca2+ loading in neonatal rabbit cardiac ventricular myocytes
American Journal of Physiology - Cell Physiology
DOI: 10.1152/ajpcell.00226.2005
2006

CDNA cloning and expression of the cardiac Na+/Ca2+ exchanger from mozambique tilapia (Oreochromis mossambicus) reveal a teleost membrane transporter with mammalian temperature dependence
Journal of Biological Chemistry
DOI: 10.1074/jbc.M504807200
2005

Na+/Ca2+ exchange activity in neonatal rabbit ventricular myocytes
American Journal of Physiology - Cell Physiology
DOI: 10.1152/ajpcell.00183.2004
2005

Phylogeny of Na+/Ca2+ exchanger (NCX) genes from genomic data identifies new gene duplications and a new family member in fish species
Physiological Genomics
DOI: 10.1152/physiolgenomics.00286.2004
2005

Increasing mammalian cardiomyocyte contractility with residues identified in trout troponin C
Physiological Genomics
DOI: 10.1152/physiolgenomics.00007.2005
2005

Effect of Temperature on the Structure of Trout Troponin C
Biochemistry
DOI: 10.1021/bi035504z
2004

Deconvolution of confocal images of dihydropyridine and ryanodine receptors in developing cardiomyocytes
Journal of Applied Physiology
DOI: 10.1152/japplphysiol.00089.2004
2004

Effect of ß-adrenergic stimulation on the relationship between membrane potential, intracellular [Ca2+] and sarcoplasmic reticulum Ca2+ uptake in rainbow trout atrial myocytes
Journal of Experimental Biology
DOI: 10.1242/jeb.00884
2004

Na+/H+ exchange inhibition with HOE 642 improves recovery of the injured neonatal rabbit heart
Canadian Journal of Cardiology
2003

Effect of temperature and the F27W mutation on the Ca2+ activated structural transition of trout cardiac troponin C
Biochemistry
DOI: 10.1021/bi0340494
2003

Sequence mutations in teleost cardiac troponin C that are permissive of high Ca2+ affinity of site II
American Journal of Physiology - Cell Physiology
2003

Triggering of sarcoplasmic reticulum Ca2+ release and contraction by reverse mode Na+/Ca2+ exchange in trout atrial myocytes
American Journal of Physiology - Regulatory Integrative and Comparative Physiology
2003

Determinants of cardiac Na+/Ca2+ exchanger temperature dependence: NH2-terminal transmembrane segments
American Journal of Physiology - Cell Physiology
2002

Ontogeny of excitation - Contraction coupling in the mammalian heart
Comparative Biochemistry and Physiology - A Molecular and Integrative Physiology
DOI: 10.1016/S1095-6433(02)00128-9
2002

Beating the cold: The functional evolution of troponin C in teleost fish
Comparative Biochemistry and Physiology - A Molecular and Integrative Physiology
DOI: 10.1016/S1095-6433(02)00046-6
2002

Temperature dependence of cardiac Na+/Ca2+ exchanger
Annals of the New York Academy of Sciences
2002

Temperature dependence of cloned mammalian and salmonid cardiac NA+/CA2+ exchanger isoforms
American Journal of Physiology - Cell Physiology
2001

Ca2+ binding to cardiac troponin C: Effects of temperature and pH on mammalian and salmonid isoforms
American Journal of Physiology - Regulatory Integrative and Comparative Physiology
2000

Evolutionary and physiological variation in cardiac troponin C in relation to thermal strategies of fish
Physiological and Biochemical Zoology
DOI: 10.1086/318095
2000

Effects of diabetes and hypertension on myocardial Na+-Ca2+ exchange
Canadian Journal of Physiology and Pharmacology
2000

Colocalization of dihydropyridine and ryanodine receptors in neonate rabbit heart using confocal microscopy
American Journal of Physiology - Heart and Circulatory Physiology
2000

Cloning, expression, and characterization of the trout cardiac Na+/Ca2+ exchanger
American Journal of Physiology - Cell Physiology
1999

Cloning and sequencing of complementary DNA for fatty acid binding protein from rainbow trout heart
Comparative Biochemistry and Physiology - B Biochemistry and Molecular Biology
DOI: 10.1016/S0305-0491(97)00309-X
1998

Dihydropyridine and ryanodine binding in ventricles from rat, trout, dogfish and hagfish
Journal of Experimental Biology
1996

Cloning and expression of salmon cardiac troponin C: Titration of the low-affinity Ca2+-binding site using a tryptophan mutant
Biochemistry
DOI: 10.1021/bi9607057
1996

Effects of doxorubicin, 4'-epirubicin, and antioxidant enzymes on the contractility of isolated cardiomyocytes
Canadian Journal of Physiology and Pharmacology
DOI: 10.1139/cjpp-74-8-904
1996

Towards a molecular explanation of the high performance of the tuna heart
Comparative Biochemistry and Physiology - A Physiology
DOI: 10.1016/0300-9629(95)02055-1
1996

cGMP elevation does not mediate muscarinic agonist-induced negative inotropy in rat ventricular cardiomyocytes
American Journal of Physiology - Heart and Circulatory Physiology
1995

Temperature and pH effects on Ca2+ sensitivity of cardiac myofibrils: A comparison of trout with mammals
American Journal of Physiology - Regulatory Integrative and Comparative Physiology
1994

Effect of temperature and temperature acclimation on the ryanodine sensitivity of the trout myocardium
Journal of Comparative Physiology B
DOI: 10.1007/BF00714580
1994

Cellular functions of diabetic cardiomyocytes: Contractility, rapid- cooling contracture, and ryanodine binding
American Journal of Physiology - Heart and Circulatory Physiology
1994

Temperature dependence of unitary properties of an ATP-dependent potassium channel in cardiac myocytes
Biophysical Journal
1993

Characterization of myocardial Na+-Ca2+ exchange in rainbow trout
American Journal of Physiology - Cell Physiology
1992

6 Excitation-Contraction Coupling in the Teleost Heart
Fish Physiology
DOI: 10.1016/S1546-5098(08)60336-2
1992

Regulation of myocardial contractility
Medicine and Science in Sports and Exercise
1991

Ca2+ transport in myocardial sarcolemma from rainbow trout
American Journal of Physiology - Regulatory Integrative and Comparative Physiology
1990

Ca<sup>2+</sup> transport across the plasma membrane of striated muscle
Medicine and Science in Sports and Exercise
1989

Effects of active oxygen generated by DTT Fe2+ on cardiac Na+ Ca2+ exchange and membrane permeability to Ca2+
Journal of Molecular and Cellular Cardiology
DOI: 10.1016/0022-2828(89)90799-2
1989

Na+-Ca2+ exchange in cardiac sarcolemma: Modulation of Ca2+ affinity by exercise
American Journal of Physiology - Cell Physiology
1989

Na+-Ca2+ exchange in cardiac sarcolemma: modulation of Ca2+ affinity by exercise.
The American journal of physiology
1989

The effect of activity on calcium-mediated events in striated muscle
Exercise and Sport Sciences Reviews
1988

Active oxygen in neuromuscular disorders
Molecular and Cellular Biochemistry
DOI: 10.1007/BF00421055
1988

Regulation of myocardial contractility in exhaustive exercise
Medicine and Science in Sports and Exercise
1985

Na+-dependent alkaline earth metal uptake in cardiac sarcolemmal vesicles
BBA - Biomembranes
DOI: 10.1016/0005-2736(85)90035-5
1985

Cardiac sarcolemma: Compositional adaptation to exercise
Science
1981

Characterization of rat myocardial sarcolemma
Journal of Molecular and Cellular Cardiology
DOI: 10.1016/0022-2828(81)90295-9
1981

Influence of exercise on excitation-contraction coupling in rat myocardium
American Journal of Physiology - Heart and Circulatory Physiology
1981

Influence of exercise on excitation-contraction coupling in rat myocardium.
The American journal of physiology
1981

Adaptation of the rat myocardium to endurance training
Journal of Applied Physiology Respiratory Environmental and Exercise Physiology
1978

Research

Regulation of cardiac myofilament sensitivity to calcium
Heart and Stroke Foundation funded project that addresses the structure function relationship of troponin C and its ability to bind Ca2+, a primary determinant of cardiac contractility. The research involves making mutations of troponin C and understanding how the structural changes that result affect Ca2+ binding to the regulatory domain of the molecule. Information from this project will be directed to the development of a novel class of Ca2+-senstizing drugs which may be used to treat heart failure.

Ontogeny of myocardial excitation- contraction coupling mechanisms
CIHR funded project with the objectives of determining the molecular and cellular changes in cardiomyocytes from the earliest stages post-partum until adulthood with an eye to understanding certain congenital heart diseases.

Molecular mechanisms of electrogenesis in the neonate heart
CIHR funded project focusing on the molecular and cellular mechansms of junctional ectopic tachycardia (JET). JET is an arrhythmia that occurs with relatively high frequency in neonates after open heart surgery. The etiology of JET is poorly understood and as a consequence existing treatments are non-specific and often lack efficacy.

Grants

NSERC Discovery Grant - Project: "Regulation of contractility in the teleost heart" (2014)

Honours & Awards

Tier I Canada Research Chair in Molecular Cardiac Physiology

Research Group Members

Jasmine Gill, Research Assistant
Marvin Gunawan, Research Assistant
Eric Lin
Lisa Lin, Graduate Student
Sabi Sangha, Research Assistant
Sanam Shafaattalab, Postdoc
Jing Wang, Lab Manager
Kevin Ye, Graduate Student, Graduate Student