Feeling the heat: source–sink mismatch as a mechanism underlying the failure of thermal tolerance

Abstract

A mechanistic explanation for the tolerance limits of animals at high temperatures is still missing, but one potential target for thermal failure is the electrical signaling off cells and tissues. With this in mind, here I review the effects of high temperature on the electrical excitability of heart, muscle and nerves, and refine a hypothesis regarding high temperature-induced failure of electrical excitation and signal transfer [the temperature-dependent deterioration of electrical excitability (TDEE) hypothesis]. A central tenet of the hypothesis is temperature-dependent mismatch between the depolarizing ion current (i.e. source) of the signaling cell and the repolarizing ion current (i.e. sink) of the receiving cell, which prevents the generation of action potentials (APs) in the latter. A source–sink mismatch can develop in heart, muscles and nerves at high temperatures owing to opposite effects of temperature on source and sink currents. AP propagation is more likely to fail at the sites of structural discontinuities, including electrically coupled cells, synapses and branching points of nerves and muscle, which impose an increased demand of inward current. At these sites, temperature-induced source–sink mismatch can reduce AP frequency, resulting in low-pass filtering or a complete block of signal transmission. In principle, this hypothesis can explain a number of heat-induced effects, including reduced heart rate, reduced synaptic transmission between neurons and reduced impulse transfer from neurons to muscles. The hypothesis is equally valid for ectothermic and endothermic animals, and for both aquatic and terrestrial species. Importantly, the hypothesis is strictly mechanistic and lends itself to experimental falsification.

Adrenergic tone benefits cardiac performance and warming tolerance in two teleost fishes that lack a coronary circulation

“…Acute warming typically results in elevated heart rate and cardiac output, but at temperatures approaching the upper thermal tolerance limit (here defined by the critical thermal maximum, CT max , in turn defined as the temperature at which the animal loses equilibrium (Beitinger et al 2000)), a plateau and subsequent reduction in heart rate and cardiac output is often observed (Ekström et al 2014;Ekström et al 2016a;Heath and Hughes 1973;Hughes and Roberts 1970;Gollock et al 2006). This decline in heart rate has been interpreted as cardiac failure in fish approaching CT max , and likely has multiple underlying reasons (see Eliason and Anttila 2017;Ekström et al 2016a;Iftikar and Hickey 2013;Haverinen and Vornanen 2020;Vornanen 2020). First, the venous oxygen tension declines as temperature rises (i.e., venous hypoxemia), which results in a reduced partial pressure gradient for oxygen diffusion into the spongy myocardium.…”

Ionic basis of atrioventricular conduction: ion channel expression and sarcolemmal ion currents of the atrioventricular canal of the rainbow trout (Oncorhynchus mykiss) heart

“…In particular, the small contact area between AV-ven and the ventricle proper is a potential site for AV block during acute heat stress. When a small cell/tissue mass (AV-ven) meets a much larger cell/tissue mass (ventricle), there is unfavorable ratio between depolarizing (source) current of active AV cells and repolarizing (sink) current of resting ventricular cells, which may prevent ventricular excitation (Vornanen 2020 ). In the zebrafish heart, the AV canal appears to be connected to the endocardial trabeculae by two specific tracts, whereas the contact of the AV canal with the outer compact myocardium seems to be blocked by an insulating wedge of connective tissue (Sedmera et al 2003 ; Icardo and Colvee 2011 ).…”

Thermal tolerance and fish heart integrity: fatty acids profiles as predictors of species resilience

“…Heart failure seems to be induced by a decrease in heart rate at temperatures close to thermal maxima ( Eliason and Anttila, 2017 ; Ekström et al , 2019 ). This decline is thought to be caused by ventricular bradycardia which might be induced by changes of the electrical properties and reduced excitability of cardiomyocytes ( Haverinen and Vornanen, 2020 ; Vornanen, 2020 ). As mitochondria play a key role in cardiac excitability ( Rossi et al , 2019 ) and increases in ROS production is known to decrease excitability (reviewed in: Aggarwal and Makielski, 2013 ), we hypothesize that mitochondrial dysfunction and the upsurge in ROS efflux of fish heart mitochondria close to thermal limits ( Christen et al , 2018 ) may reduce cardiomyocytes excitability and subsequently induce bradycardia and ultimately result in heart failure.…”