Interaction of background Ca²⁺ influx, sarcoplasmic reticulum threshold and heart failure in determining propensity for Ca²⁺ waves in sheep heart

Abstract

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Background calcium influx in arrhythmia: lead actor or extra?

“…Nevertheless, although our suggestions of a possible role of background influx in the pathophysiology of AF remain highly speculative, what remains certain is that the findings of Hutchings et al (2022) pose an important question of whether background Ca 2+ influx could be a 'lead actor' in the 'cinematic' pathophysiology of arrhythmia, or an insignificant 'extra' . Therefore, further research is necessary to establish the role of background Ca 2+ influx in this 'movie' called arrhythmia.…”

“…Interestingly, in addition to the study outcome exempting the contribution of NCX to the observed background Ca 2+ influx via its reverse mode Na + /Ca 2+ exchange, Hutchings et al. (2022) demonstrated that connexins and some members of the TRPC family, that is TRPC1/4/5, did not contribute to the background influx responsible for the SR Ca 2+ overload in the sheep ventricular myocytes. Instead, TRPC6 was found to be a key contributor to the background Ca 2+ entry in ventricular myocytes exposed to elevated extracellular Ca 2+ .…”

“…Background Ca 2+ influx denotes Ca 2+ entry into myocytes in an unstimulated or resting state. Mechanisms mediating this background Ca 2+ influx are still fragmentary; however, connexin hemichannels, STIM1‐mediated Ca 2+ entry and transient receptor potential canonical (TRPC) channels have been documented to contribute to this background entry of Ca 2+ (Hulot et al., 2011; Hutchings et al., 2022). Interestingly, in addition to the study outcome exempting the contribution of NCX to the observed background Ca 2+ influx via its reverse mode Na + /Ca 2+ exchange, Hutchings et al.…”

The role of background calcium influx on heart failure‐associated calcium waves: what you do not know, you do not recognise

“…However, Hutchings et al. (2022) nicely revealed that SR Ca 2+ overload and spontaneous Ca 2+ waves induced by such supra‐physiological levels of [Ca 2+ ] o were due primarily to TRPC6‐mediated Ca 2+ influx instead of LTCC and NCX. The pronounced effect of high [Ca 2+ ] o on spontaneous Ca 2+ waves supports the pro‐arrhythmic effect of hypercalcaemia in HF.…”

“…In a recent study published in The Journal of Physiology , Hutchings et al. (2022) investigated the mechanisms underlying cardiomyocyte Ca 2+ entry in the presence of high concentrations of extracellular Ca 2+ ([Ca 2+ ] o ) and its contribution to the generation of spontaneous Ca 2+ waves in a large‐animal HF model. HF was induced in sheep by right‐ventricular tachypacing and diagnosed based on symptoms (i.e.…”