Excitation-Contraction Coupling in Zebrafish Ventricular Myocardium Is Regulated by Trans-Sarcolemmal Ca2+ Influx and Sarcoplasmic Reticulum Ca2+ Release

Haustein, Moritz; Hannes, Tobias; Trieschmann, Jan; Verhaegh, Rabea; Köster, Annette; Hescheler, Jürgen; Brockmeier, Konrad; Adelmann, Roland; Khalil, Markus

doi:10.1371/journal.pone.0125654

Cited by 14 publications

(10 citation statements)

References 31 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A flat or negative FFR is a hallmark of HF ( Pieske et al, 1998 ). Conversely, FFR is strongly negative in the zebrafish heart ( Haustein et al, 2015 ), likely mainly due to low dependence of excitation-contraction coupling on SR calcium cycling. These differences need to be acknowledged when modeling human HF.…”

Section: Discussionmentioning

confidence: 99%

Zebrafish Heart Failure Models

Narumanchi

Wang

Perttunen

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Heart failure causes significant morbidity and mortality worldwide. The understanding of heart failure pathomechanisms and options for treatment remain incomplete. Zebrafish has proven useful for modeling human heart diseases due to similarity of zebrafish and mammalian hearts, fast easily tractable development, and readily available genetic methods. Embryonic cardiac development is rapid and cardiac function is easy to observe and quantify. Reverse genetics, by using morpholinos and CRISPR-Cas9 to modulate gene function, make zebrafish a primary animal model for in vivo studies of candidate genes. Zebrafish are able to effectively regenerate their hearts following injury. However, less attention has been given to using zebrafish models to increase understanding of heart failure and cardiac remodeling, including cardiac hypertrophy and hyperplasia. Here we discuss using zebrafish to study heart failure and cardiac remodeling, and review zebrafish genetic, drug-induced and other heart failure models, discussing the advantages and weaknesses of using zebrafish to model human heart disease. Using zebrafish models will lead to insights on the pathomechanisms of heart failure, with the aim to ultimately provide novel therapies for the prevention and treatment of heart failure.

show abstract

Section: Discussionmentioning

confidence: 99%

Zebrafish Heart Failure Models

Narumanchi

Wang

Perttunen

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…All the kinetic parameters, such as the RT, FT, and HD of the Ca 2+ transients became faster ( Figures 6G–J ) as observed in other fish models ( Lin et al, 2015 ; Rayani et al, 2018 ). In terms of the negative staircase behavior of Ca 2+ transients, there are reports for other fish models related to a decrease in the amplitude of Ca 2+ transients ( Lin et al, 2015 ) and in developed pressure ( Haustein et al, 2015 ). Interestingly, although mice display a significant negative staircase profile in the amplitude of the Ca 2+ transients ( Kornyeyev et al, 2012 ), larger mammals present a positive staircase profile in their mechanical response ( Langer, 1967 ; Kodama et al, 1981 ; Opitz, 1980 ; Bouchard and Bose, 1989 ; Hattori et al, 1991 ).…”

Section: Discussionmentioning

confidence: 99%

Excitation–Contraction Coupling in the Goldfish (Carassius auratus) Intact Heart

Bazmi

Escobar

2020

Front. Physiol.

View full text Add to dashboard Cite

Cardiac physiology of fish models is an emerging field given the ease of genome editing and the development of transgenic models. Several studies have described the cardiac properties of zebrafish ( Denio rerio ). The goldfish ( Carassius auratus ) belongs to the same family as the zebrafish and has emerged as an alternative model with which to study cardiac function. Here, we propose to acutely study electrophysiological and systolic Ca 2+ signaling in intact goldfish hearts. We assessed the Ca 2+ dynamics and the electrophysiological cardiac function of goldfish, zebrafish, and mice models, using pulsed local field fluorescence microscopy, intracellular microelectrodes, and flash photolysis in perfused hearts. We observed goldfish ventricular action potentials (APs) and Ca 2+ transients to be significantly longer when compared to the zebrafish. The action potential half duration at 50% (APD 50 ) of goldfish was 370.38 ± 8.8 ms long, and in the zebrafish they were observed to be only 83.9 ± 9.4 ms. Additionally, the half duration of the Ca 2+ transients was also longer for goldfish (402.1 ± 4.4 ms) compared to the zebrafish (99.1 ± 2.7 ms). Also, blocking of the L-type Ca 2+ channels with nifedipine revealed this current has a major role in defining the amplitude and the duration of goldfish Ca 2+ transients. Interestingly, nifedipine flash photolysis experiments in the intact heart identified whether or not the decrease in the amplitude of Ca 2+ transients was due to shorter APs. Moreover, an increase in temperature and heart rate had a strong shortening effect on the AP and Ca 2+ transients of goldfish hearts. Furthermore, ryanodine (Ry) and thapsigargin (Tg) significantly reduced the amplitude of the Ca 2+ transients, induced a prolongation in the APs, and altogether exhibited the degree to which the Ca 2+ release from the sarcoplasmic reticulum contributed to the Ca 2+ transients. We conclude that the electrophysiological properties and Ca 2+ signaling in intact goldfish hearts strongly resembles the endocardial layer of larger mammals.

show abstract

“…It has been reported that verapamil has the potential to change myocardial Ca 2+ sensitivity in zebrafish and the mechanism by which this occurs may involve myofilament Ca 2+ sensitivity of the heart muscle (Haustein et al ., 2015). A potential mechanism for the effects of ketamine and ALCAR on mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) linked to Ca 2+ in zebrafish was discussed in our previous study (Kanungo et al ., 2012).…”

Section: Discussionmentioning

confidence: 99%

Acetyl L‐carnitine targets adenosine triphosphate synthase in protecting zebrafish embryos from toxicities induced by verapamil and ketamine: An in vivo assessment

Guo

Dumas

Robinson

et al. 2016

J of Applied Toxicology

View full text Add to dashboard Cite

Verapamil is a Ca2+ channel blocker and is highly prescribed as an anti-anginal, antiarrhythmic and antihypertensive drug. Ketamine, an antagonist of the Ca2+-permeable N-methyl-D-aspartate-type glutamate receptors, is a pediatric anesthetic. Previously we have shown that acetyl L-carnitine (ALCAR) reverses ketamine-induced attenuation of heart rate and neurotoxicity in zebrafish embryos. Here, we used 48 h post-fertilization zebrafish embryos that were exposed to relevant drugs for 2 or 4 h. Heart beat and overall development were monitored in vivo. In 48 h post-fertilization embryos, 2 mM ketamine reduced heart rate in a 2 or 4 h exposure and 0.5 mM ALCAR neutralized this effect. ALCAR could reverse ketamine’s effect, possibly through a compensatory mechanism involving extracellular Ca2+ entry through L-type Ca2+ channels that ALCAR is known to activate. Hence, we used verapamil to block the L-type Ca2+ channels. Verapamil was more potent in attenuating heart rate and inducing morphological defects in the embryos compared to ketamine at specific times of exposure. ALCAR reversed cardiotoxicity and developmental toxicity in the embryos exposed to verapamil or verapamil plus ketamine, even in the presence of 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester, an inhibitor of intracellular Ca2+ release suggesting that ALCAR acts via effectors downstream of Ca2+. In fact, ALCAR’s protective effect was blunted by oligomycin A, an inhibitor of adenosine triphosphate synthase that acts downstream of Ca2+ during adenosine triphosphate generation. We have identified, for the first time, using in vivo studies, a downstream effector of ALCAR that is critical in abrogating ketamine- and verapamil-induced developmental toxicities. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

show abstract

Excitation-Contraction Coupling in Zebrafish Ventricular Myocardium Is Regulated by Trans-Sarcolemmal Ca2+ Influx and Sarcoplasmic Reticulum Ca2+ Release

Cited by 14 publications

References 31 publications

Zebrafish Heart Failure Models

Zebrafish Heart Failure Models

Excitation–Contraction Coupling in the Goldfish (Carassius auratus) Intact Heart

Acetyl L‐carnitine targets adenosine triphosphate synthase in protecting zebrafish embryos from toxicities induced by verapamil and ketamine: An in vivo assessment

Contact Info

Product

Resources

About