Ionic channels underlying the ventricular action potential in zebrafish embryo

Alday, Aintzane; Alonso, Hiart; Gallego, Mónica; Urrutia, Janire; Letamendı́a, Ainhoa; Callol, Carles; Casis, Óscar

doi:10.1016/j.phrs.2014.03.011

Cited by 38 publications

(43 citation statements)

References 33 publications

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“…In fish, the HO-1/CO pathway plays a dilatory role in blood vessels via a CO-mediated increase in cGMP (Dombkowski et al, 2009). Other CO targets may include ion channels such as voltage-gated Ca 2+ (T-type Ca 2+ channels; reviewed in Capel and Terrar, 2015) and K + channels (HCN and ERG K + channels) important for establishing the robust T-type Ca 2+ current coupled with a 'funny' current (I f ) and a rapid delayed rectifier K + current (I Kr ) that are important for the diastolic depolarization rate of the developing zebrafish heart (Nemtsas et al, 2010;Alday et al, 2014). Studies from mammals have shown that endogenous CO inhibits all isoforms of T-type Ca 2+ channels as well as ERG K + channels (responsible for I Kr ) under normoxic conditions (reviewed in Peers et al, 2015) but there is no information on the effect of endogenous CO on HCN channels (responsible for I f ).…”

Section: Presence Of Ho-1 In the Hearts Of Fishmentioning

confidence: 99%

Evidence for a role of heme oxygenase-1 in the control of cardiac function in zebrafish (Danio rerio) larvae exposed to hypoxia

Tzaneva

Perry

2016

Journal of Experimental Biology

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Carbon monoxide (CO) is a gaseous neurotransmitter produced from the breakdown of heme via heme oxygenase-1 (HO-1; hypoxiainducible isoform) and heme oxygenase-2 (HO-2; constitutively expressed isoform). In mammals, CO is involved in modulating cardiac function. The role of the HO-1/CO system in the control of heart function in fish, however, is unknown and investigating its physiological function in lower vertebrates will provide a better understanding of the evolution of this regulatory mechanism. We explored the role of the HO-1/CO system in larval zebrafish (Danio rerio) in vivo by investigating the impact of translational gene knockdown of HO-1 on cardiac function. Immunohistochemistry revealed the presence of HO-1 in the pacemaker cells of the heart at 4 days post-fertilization and thus the potential for CO production at these sites. Sham-treated zebrafish larvae (experiencing normal levels of HO-1) significantly increased heart rate ( f H ) when exposed to hypoxia (Pw O2 =30 mmHg). Zebrafish larvae lacking HO-1 expression after morpholino knockdown (morphants) exhibited significantly higher f H under normoxic (but not hypoxic) conditions when compared with sham-treaded fish. The increased f H in HO-1 morphants was rescued ( f H was restored to control levels) after treatment of larvae with a CO-releasing molecule (40 µmol l −1 CORM). The HO-1-deficient larvae developed significantly larger ventricles and when exposed to hypoxia they displayed higher cardiac output ( _ Q) and stroke volume (SV). These results suggest that under hypoxic conditions, HO-1 regulates _ Q and SV presumably via the production of CO. Overall, this study provides a better understanding of the role of the HO-1/CO system in controlling heart function in lower vertebrates. We demonstrate for the first time the ability for CO to be produced in presumptive pacemaker cells of the heart where it plays an inhibitory role in setting the resting cardiac frequency.

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Section: Presence Of Ho-1 In the Hearts Of Fishmentioning

confidence: 99%

Evidence for a role of heme oxygenase-1 in the control of cardiac function in zebrafish (Danio rerio) larvae exposed to hypoxia

Tzaneva

Perry

2016

Journal of Experimental Biology

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“… 1 (Vornanen & Hassinen, ) 2 (Vornanen et al ., ) 3 (Dibb et al ., ) 4 (Moosmang et al ., ) 5 (Nemtsas et al ., ) 6 (Ma et al ., ) 7 (Fermini et al ., ) 8 (Noble & Tsien, ) 9 (Huang, ) 10 (European Medicines Agency, ) 11 (Warren et al ., ) 12 (Abramochkin et al ., ) 13 (Boyett, ) 14 (Bovo et al ., ) 15 (Alday et al ., ) 16 (Nakamura & Coetzee, ) 17 (Weidmann, ) 18 (Lopatin & Nichols, )…”

Section: Introductionmentioning

confidence: 99%

Polyaromatic hydrocarbons in pollution: a heart‐breaking matter

Marris

Kompella

Miller

et al. 2020

The Journal of Physiology

123

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Air pollution is associated with detrimental effects on human health, including decreased cardiovascular function. However, the causative mechanisms behind these effects have yet to be fully elucidated. Here we review the current epidemiological, clinical and experimental evidence linking pollution with cardiovascular dysfunction. Our focus is on particulate matter (PM) and the associated low molecular weight polycyclic aromatic hydrocarbons (PAHs) as key mediators of cardiotoxicity. We begin by reviewing the growing epidemiological evidence linking air pollution to cardiovascular dysfunction in humans. We next address the pollution‐based cardiotoxic mechanisms first identified in fish following the release of large quantities of PAHs into the marine environment from point oil spills (e.g. Deepwater Horizon). We finish by discussing the current state of mechanistic knowledge linking PM and PAH exposure to mammalian cardiovascular patho‐physiologies such as atherosclerosis, cardiac hypertrophy, arrhythmias, contractile dysfunction and the underlying alterations in gene regulation. Our aim is to show conservation of toxicant pathways and cellular targets across vertebrate hearts to allow a broad framework of the global problem of cardiotoxic pollution to be established. AhR; Aryl hydrocarbon receptor. Dark lines indicate topics discussed in this review. Grey lines indicate topics reviewed elsewhere.

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“…While AT II antagonists do not impact cardiac de-and repolarisation, 17 this is not finally resolved for calcium channel blockers. 18,19 Limitations of this study are the small number of patients as well Among triazole antifungal agents, QTc shortening by isavuconazole is unique and so far has not been associated with untoward cardiovascular events. Knowledge about cardiac effects of isavuconazole will serve to better manage the use of concomitant medications.…”

Section: Discussionmentioning

confidence: 96%

“…Regarding co‐medication, amlodipine (calcium channel blocker) and valsartan (AT II antagonist) were newly prescribed in the time span of first and second ECG. While AT II antagonists do not impact cardiac de‐ and repolarisation, this is not finally resolved for calcium channel blockers …”

Section: Discussionmentioning

confidence: 99%

Isavuconazole shortens the QTc interval

Mellinghoff

Bassetti

Dörfel

et al. 2018

Mycoses

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Isavuconazole is a novel antifungal drug approved for the treatment of adults with invasive aspergillosis and mucormycosis. While azoles as a class effect are known to prolong QTc interval, clinical trials have shown that isavuconazole administration may cause shortening in a dose-related manner. Here, we assessed the effects of isavuconazole on the length of QTc interval. The objective of the study was to describe changes in the QTc interval induced by isavuconazole treatment. A total of 26 adult patients from 7 hospitals were included. Patients received isavuconazole for the treatment of invasive fungal infection and, in 1 case, for prophylaxis due to QTc prolongation under fluconazole. Twelve-channel electrocardiograms (ECGs) were performed before and during treatment. Out of 26 patients, 24 showed shortening of QTc interval. In patients with QTc shortening, QTc during isavuconazole treatment showed a mean decrease of 7.4 ± 5.8% (36.5 ± 38.8 ms, range 7-202; P = .004), compared to pre-isavuconazole ECG. One patient with available long-term follow-up showed further decrease in QTc on days 55 and 110. Apart from 1 case report, these are the first data outside controlled clinical trials showing QTc shortening. Knowledge about cardiac effects of isavuconazole will serve to better manage the use of concomitant medications.

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Ionic channels underlying the ventricular action potential in zebrafish embryo

Cited by 38 publications

References 33 publications

Evidence for a role of heme oxygenase-1 in the control of cardiac function in zebrafish (Danio rerio) larvae exposed to hypoxia

Evidence for a role of heme oxygenase-1 in the control of cardiac function in zebrafish (Danio rerio) larvae exposed to hypoxia

Polyaromatic hydrocarbons in pollution: a heart‐breaking matter

Isavuconazole shortens the QTc interval

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