# Thermal plasticity of adrenaline-mediated, frequency-dependent calcium homeostasis in rainbow trout ventricular cardiomyocytes

## TL;DR

This study explores how sudden temperature increases affect heart cell calcium balance in rainbow trout, revealing that thermal stress disrupts heart function mechanisms.

## Contribution

The study reveals how acute warming and adrenaline interact to affect calcium homeostasis in trout heart cells, offering new insights into thermal stress impacts.

## Key findings

- Adrenaline had a positive inotropic effect at both 10°C and 22°C, but was less effective at the higher temperature.
- SR inhibition was associated with irregular calcium transients, suggesting disrupted calcium cycling.
- Acute thermal stress may disrupt calcium homeostasis in trout cardiomyocytes, potentially affecting heart contractility.

## Abstract

The effect of global warming on rising aquatic temperatures is producing ever-steeper thermoclines. Fish encountering these sharp changes in water temperature might experience an acute-warming stress. Temperature is the most dominant environmental factor affecting heart function in fish, and without compensatory mechanisms as temperatures rise (e.g. higher heart rate), it could imperil cardiovascular performance. To enhance heart function during acute warming, fish release adrenaline to boost Ca2+ influx in heart cells (cardiomyocytes). However, the relationship between acute warming, elevated heart rate, adrenergic stimulation and intracellular Ca2+ handling is not well understood at the cellular level. In this study, we investigated the interplay between these key functional drivers in isolated ventricular cardiomyocytes of rainbow trout, at either their acclimation temperature of 10°C or following acute warming (22°C). A subset of cardiomyocytes from each group was treated with adrenaline, sarcoplasmic reticulum (SR) inhibitors (that inhibit intracellular Ca2+ cycling via the SR) or both, whereas pacing frequency was simultaneously increased (simulating faster heart rate). Using epifluorescent microscopy, we measured intracellular Ca2+ transients (Δ[Ca2+]i) and Ca2+-cycling kinetics. Across all pacing frequencies, we found no differences in Δ[Ca2+]i between control (untreated) 10°C and 22°C cardiomyocytes, and that adrenaline had a positive inotropic effect at both temperatures, but was less effective at 22°C. SR inhibition had no effect on Δ[Ca2+]i, but was associated with a greater incidence of irregular Δ[Ca2+]i. Our data suggest that acute thermal stress can disrupt Ca2+-homeostatic mechanisms in trout cardiomyocytes, potentially disrupting whole-heart contractility as global temperatures rise.

Summary: Analysis of the relationship between acute warming, elevated heart rate, adrenaline and inhibited SR intracellular Ca2+ cycling shows that acute thermal stress disrupts mechanisms regulating Ca2+ homeostasis in trout cardiomyocytes, which might underlie disruption of whole-heart contractility.