Figure 3. Conceptual framework of S100A1 target structures in cardiomyocytes.

(A) S100A1 protein interacts with RyR2, resulting in enhanced systolic SR Ca²⁺ release, improved EC-coupling gain and prevention of arrhythmogenic diastolic Ca²⁺ leakage. (B) Augmented systolic SR Ca²⁺ release is compensated by elevated SERCA2a activity, leading to accelerated removal of cytosolic Ca²⁺ and increased SR Ca²⁺ load. (C) S100A1 interaction with mitochondria enhances mitochondrial ATP retrieval, matching increased energy demands. (D) S100A1 interference with titin-actin interplay decreases myofilament stiffness and facilitates diastolic Ca²⁺ dissociation, alleviating passive tension and diastolic relaxation of the contractile apparatus.

LTCC: L-type calcium channel; NCX: Sodium-calcium exchanger; RyR2: ryanodine receptor 2; SERCA: Sarcoplasmic/endoplasmic reticulum calcium ATPase; SR: Sarcoplasmic reticulum.

Reproduced with permission from [6].