Ca²⁺ signalling in cardiac muscle: the importance of balances

In this narrative review, an example of a cardiac arrhythmia with a mechanistically appealing molecular pathomechanism is highlighted. This example will be used to delineate how recent basic science findings, which are summarized, can be used to obtain a deeper understanding of pathological behaviour from the molecular to the cellular level. The condition in question is the highly lethal catecholaminergic polymorphic ventricular tachycardia resulting from a point mutation of the cardiac ryanodine receptor. For this deep dive, the RyR2^R420Q phenotype will be discussed in detail. Interestingly, these findings and the conclusions which could be drawn from them were very much unexpected but could be relevant for pharmacological treatments. To make the transition from the molecular and cellular findings to the patient will require the translation across several layers of complexity. Ultimately, such detailed understanding will lead to improved therapies tailored to each individual case and the specific RyR2 mutation carried by a particular family, in the framework of precision medicine.