Abstract Background The electromechanical function of myocardial tissue depends on the intercellular communication between cardiomyocytes (CMs) as well as their crosstalk with other cell types. Cell injury, and subsequent death trigger inflammation as in myocardial infarction (MI) resulting in myocardial remodeling. Although mechanisms underlying myocardial cell death have been studied so far, the signaling events following single cell death and spontaneous response of connected cells in the myocardial tissue is still barely understood. Methods Here, we investigated the effect of laser-induced single cell death on Calcium (Ca²⁺) concentrations and transport in myocardial cell clusters in vitro. Spatial and temporal changes in intracellular Ca²⁺ concentrations [Ca²⁺]_i were studied using a fluorescent calcium indicator, Fluo-4AM. Spontaneous signaling events following cell death were studied in rat embryonic cardiomyocytes and non-myocytes using separate cell culture systems. Results Cell death triggered spontaneous increase in intracellular Ca²⁺ levels ([Ca²⁺]_i) of surrounding cells. The spread of the observed propagating Ca²⁺ signal was slow and sustained in myocytes while it was rapid and transient in fibroblasts (Fbs). Further, sustained high Ca²⁺ levels temporarily impaired the contractility in CMs. The cell-type specific effect of ablation was confirmed using separate cultures of CMs and Fbs. Comparing Ca²⁺ propagation speed in myocytes and fibroblasts, we argue for a diffusion-driven Ca²⁺ propagation in myocytes, but not in fibroblasts. Radial and sequential Ca²⁺ diffusion across the CMs through cell–cell contacts and presence of Cx43-based intercellular junctions indicated a gap junction flow of Ca²⁺. Conclusions These findings illustrate the spontaneous Ca²⁺-mediated functional interplay in myocardial cell clusters upon mechanical injury and, further, the difference in Ca²⁺ signaling in cardiomyocytes and fibroblasts.