Cardiomyocyte Morphology and Physiology

Shiels, Holly A.

doi:10.1016/bs.fp.2017.04.001

Cited by 9 publications

(8 citation statements)

References 155 publications

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“…In pacemaker cardiomyocytes, such an increase in cAMP would be expected to activate hyperpolarization‐activated cyclic nucleotide–gated (HCN) channels, which are known to determine heart rate in larval zebrafish, 49 and increase heart rate. The possible stimulatory effect of ß2‐ARs is consistent with decades of research suggesting that ß2‐ARs are primarily responsible for the binding of catecholamines and positive inotropic effect on atrial and ventricular myocardium in other fish species 25–30 . Given that both positive chronotropic and positive inotropic effects largely stem from similar mechanisms dependent on cAMP accumulation, it is reasonable to predict that ß2‐ARs could exert stimulatory effects in pacemaker, atrial, and ventricular cardiomyocytes alike.…”

Section: Discussionsupporting

confidence: 73%

“…Although the results of some previous studies 15,23,24 suggested that the ß1‐AR (encoded by adrb1 ) is largely responsible for positive chronotropic effects of adrenergic stimulation in zebrafish, as is believed to be the case in mammals, 33 this notion is in contrast to the long held dogma that ß2‐ARs dominate in the fish heart 28 . Our results indicate that, while deletion of adrb1 reduces routine heart rate, it is not essential for positive chronotropic responses to pharmacological adrenergic stimulation or environmental stressors that increase adrenergic tone.…”

Section: Discussionmentioning

confidence: 92%

“…In 5 dpf larvae, adrb1 knockdown and ß1‐AR‐specific antagonist atenolol abolished the tachycardia in response to elevated CO 2 (hypercapnia) exposure 23 while atenolol reduced heart rate and cardiac contractility in adult zebrafish hearts 24 . These data are somewhat surprising as previous studies suggested that ß2‐ARs are dominantly expressed in atrium and ventricle in other teleost fish species 25–30 . Moreover, an immunohistological investigation showed abundant ß2‐AR protein expression across the zebrafish heart, including the SAN region 16 …”

Section: Introductionmentioning

confidence: 92%

“…24 These data are somewhat surprising as previous studies suggested that ß2-ARs are dominantly expressed in atrium and ventricle in other teleost fish species. [25][26][27][28][29][30] Moreover, an immunohistological investigation showed abundant ß2-AR protein expression across the zebrafish heart, including the SAN region. 16 Pharmacological and morpholino knockdown approaches can be limited by non-specific and off-target effects.…”

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confidence: 99%

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Regulation of heart rate following genetic deletion of the ß1 adrenergic receptor in larval zebrafish

et al. 2022

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Aim Although zebrafish are gaining popularity as biomedical models of cardiovascular disease, our understanding of their cardiac control mechanisms is fragmentary. Our goal was to clarify the controversial role of the ß1‐adrenergic receptor (AR) in the regulation of heart rate in zebrafish. Methods CRISPR‐Cas9 was used to delete the adrb1 gene in zebrafish allowing us to generate a stable adrb1−/− line. Larval heart rates were measured during pharmacological protocols and with exposure to hypercapnia. Expression of the five zebrafish adrb genes were measured in larval zebrafish hearts using qPCR. Results Compared with genetically matched wild‐types (adrb1+/+), adrb1−/− larvae exhibited ~20 beats min−1 lower heart rate, measured from 2 to 21 days post‐fertilization (dpf). Nevertheless, adrb1−/− larvae exhibited preserved positive chronotropic responses to pharmacological treatment with AR agonists (adrenaline, noradrenaline, isoproterenol), which were blocked by propranolol (general ß‐AR antagonist). Regardless of genotype, larvae exhibited similar increases in heart rate in response to hypercapnia (1% CO2) at 5 dpf, but tachycardia was blunted in adrb1−/− larvae at 6 dpf. adrb1 gene expression was abolished in the hearts of adrb1−/− larvae, confirming successful knockout. While gene expression of adrb2a and adrb3a was unchanged, adrb2b and adrb3b mRNA levels increased in adrb1−/− larval hearts. Conclusion Despite adrb1 contributing to the setting of resting heart rate in larvae, it is not strictly essential for zebrafish, as we generated a viable and breeding adrb1−/− line. The chronotropic effects of adrenergic stimulation persist in adrb1−/− zebrafish, likely due to the upregulation of other ß‐AR subtypes.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 92%

mentioning

confidence: 99%

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Regulation of heart rate following genetic deletion of the ß1 adrenergic receptor in larval zebrafish

et al. 2022

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“…Adrenaline increases cardiomyocyte contractility, primarily via β-adrenergic receptors, by increasing the amplitude of the Ca 2+ transient that initiates cardiomyocyte contraction. The increase in the Ca 2+ transient is attained by increasing sarcolemmal Ca 2+ influx and augmenting Ca 2+ -induced Ca 2+ release from the sarcoplasmic reticulum via protein kinase A-dependent phosphorylation (Cros et al, 2014;Eisner et al, 2017;Shiels, 2017;Vornanen, 2017). In many species, including fish, reptiles and mammals, increasing myocardial contractility with adrenaline (such as occurs during exercise) shifts the Starling curve upwards (Fig.…”

Section: The Regulation Of Cardiac Functionmentioning

confidence: 99%

What determines systemic blood flow in vertebrates?

Joyce

Wang

2020

Journal of Experimental Biology

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In the 1950s, Arthur C. Guyton removed the heart from its pedestal in cardiovascular physiology by arguing that cardiac output is primarily regulated by the peripheral vasculature. This is counterintuitive, as modulating heart rate would appear to be the most obvious means of regulating cardiac output. In this Review, we visit recent and classic advances in comparative physiology in light of this concept. Although most vertebrates increase heart rate when oxygen demands rise (e.g. during activity or warming), experimental evidence suggests that this tachycardia is neither necessary nor sufficient to drive a change in cardiac output (i.e. systemic blood flow, Q̇sys) under most circumstances. Instead, Q̇sys is determined by the interplay between vascular conductance (resistance) and capacitance (which is mainly determined by the venous circulation), with a limited and variable contribution from heart function (myocardial inotropy). This pattern prevails across vertebrates; however, we also highlight the unique adaptations that have evolved in certain vertebrate groups to regulate venous return during diving bradycardia (i.e. inferior caval sphincters in diving mammals and atrial smooth muscle in turtles). Going forward, future investigation of cardiovascular responses to altered metabolic rate should pay equal consideration to the factors influencing venous return and cardiac filling as to the factors dictating cardiac function and heart rate.

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Cardiac Form, Function and Physiology

Farrell

Smith

2017

Fish Physiology

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Cardiomyocyte Morphology and Physiology

Cited by 9 publications

References 155 publications

Regulation of heart rate following genetic deletion of the ß1 adrenergic receptor in larval zebrafish

Regulation of heart rate following genetic deletion of the ß1 adrenergic receptor in larval zebrafish

What determines systemic blood flow in vertebrates?

Cardiac Form, Function and Physiology

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