Zebrafish as a Model of Mammalian Cardiac Function: Optically Mapping the Interplay of Temperature and Rate on Voltage and Calcium Dynamics

The zebrafish (Danio rerio) heart is a viable model of mammalian cardiovascular function due to similarities in heart rate, ultrastructure, and action potential morphology. Zebrafish are able to tolerate a wide range of naturally occurring temperatures through altering chronotropic and inotropic properties of the heart. Optical mapping of cannulated zebrafish hearts can be used to assess the effect of temperature on excitation-contraction (EC) coupling and to explore the mechanisms underlying voltage (Vm) and calcium (Ca2+) transients. Applicability of zebrafish as a model of mammalian cardiac physiology should be understood in the context of numerous subtle differences in structure, ion channel expression, and Ca2+ handling. In contrast to mammalian systems, Ca2+ release from the sarcoplasmic reticulum (SR) plays a relatively small role in activating the contractile apparatus in teleosts, which may contribute to differences in restitution. The contractile function of the zebrafish heart is closely tied to extracellular Ca2+ which enters cardiomyocytes through L-type Ca2+ channel (LTCC), T-type Ca2+ channel (TTCC), and the sodium-calcium exchanger (NCX). Novel data found that despite large temperature effects on heart rate, Vm, and Ca2+ durations, the relationship between Vm and Ca2+ signals was only minimally altered in the face of acute temperature change. This suggests that zebrafish Vm and Ca2+ kinetics are largely rate-independent. In comparison to mammalian systems, zebrafish Ca2+ cycling is inherently more dependent on transsarcolemmal Ca2+ transport and less reliant on SR Ca2+ release. However, the compensatory actions of various components of the Ca2+ cycling machinery of the zebrafish cardiomyocytes, allow for maintenance of EC coupling over a wide range of environmental temperatures

Physiological phenotyping of the adult zebrafish heart

The zebrafish has proven to be an excellent organism for manipulation of its genome from a long history of transcript down-regulation using morpholino oligimers to more recent genome editing tools such as CRISPR-Cas9. Early forward and reverse genetic screens significantly benefited from the transparency of zebrafish embryos, allowing cardiac development as a function of genetics to be directly observed. However, gradual loss of transparency with subsequent maturation limited many of these approaches to the first several days post-fertilization. As many genes are developmentally regulated, the immature phenotype is not entirely indicative of that of the mature zebrafish. For accurate phenotyping, subsequent developmental stages including full maturation must also be considered. In adult zebrafish, cardiac function can now be studied in great detail due both to the size of the hearts as well as recent technological improvements. Because of their small size, zebrafish are particularly amenable to high frequency echocardiography for detailed functional recordings. Although relatively small, the hearts are easily excised and contractile parameters can be measured from whole hearts, heart slices, individual cardiomyocytes and even single myofibrils. Similarly, electrical activity can also be measured using a variety of techniques, including in vivo and ex vivo electrocardiograms, optical mapping and traditional microelectrode techniques. In this report, the major advantages and technical considerations of these physiological tools are discussed.The grant support to GFT from the Natural Sciences and Engineering Research Council of Canada (NSERC), the Canada Foundation for Innovation and the Canada Research Chairs programs are gratefully acknowledged

Liberal Government and the Practical History of Anthropology

This paper explores the implications of Foucault's perspective of liberal government for approaches to the practical history of anthropology. It also draws on assemblage theory to consider the changing relations between field, museum and university in relation to a range of early twentieth-century anthropological practices. These focus mainly on the development of the Boasian paradigm in the USA during the inter-war years and on the anthropological practices clustered around the Musée de l'Homme in the 1930s. Key steps in the argument focus on the role of what Foucault called "transactional realities" in mediating the practical applications of anthropology in colonial contexts and in "anthropology at home" projects. Special consideration is also given to the increasingly archival properties of anthropological collections in the early twentieth century and the consequences of this for anthropology's relations to practices of governing