(A,) Summary of the processes that build up a local Ca2+ signal at t1 (Ft1), taking into account the Ca2+ signal from t0 (Ft0), its diffusion during the time t0 to t1 (blue to red trace) and additional Ca2+ release (green trace, from left to right). (B) The data pipeline and principle steps of the CaCLEAN algorithm. First, the Ca2+ release component (between t0 and t1) is deconvolved (left part). Please note that we deliberately used the term ‘release’ for simplification, knowing that the signal comprises Ca2+ influx through LTCC and Ca2+ release from the RyRs. Thereafter the centers of the couplon sites are identified (right part in dashed box). ACO, ‘Analytical CLEAN Object’.