Changes in cytosolic Ca²⁺ concentration ([Ca²⁺]_c) serve as a ubiquitous signaling mechanism that orchestrates a range of cellular functions essential for life. Our understanding of Ca²⁺ signaling has come primarily from studies of individual cellular responses using indicator dyes or genetically encoded probes such as GCaMP. These studies have revealed the intricate spatiotemporal nature of cellular and subcellular Ca²⁺ signaling, which allows for the differential control of numerous signaling cascades. Nevertheless, Ca²⁺ signals can propagate between cells at the tissue level adding additional layers of control and complexity, including coordinated signals between multiple cells and cell types that integrate the responses of intact organs.

Investigations into multicellular signaling reveal that these ions are not just intra-cellular messengers, but also mediate extensive intercellular communication via the process of intercellular Ca²⁺ wave propagation. This intercellular Ca²⁺ signaling is accomplished in different ways in non-excitable and excitable cells and tissues, but in all cases, regeneration or amplification of the original signal is essential for Ca²⁺ wave propagation and the underlying tissue function.

A range of factors, from the complex determination of the distance and frequency of [Ca²⁺]_c wave propagation to the added layer of additional endocrine and neuronal inputs in studied tissues, contribute to the complexity of imaging, analyzing, and interpreting Ca²⁺ signaling in multicellular systems. These challenges highlight the need for interdisciplinary approaches, combining advanced imaging techniques, mathematical modeling, and experimental biology.

Beyond basic science, the translational relevance of this work is significant and impactful. Dysfunctional Ca²⁺ signaling is implicated in numerous disease states, including diabetes, metabolic syndrome, and deafness. Therefore, understanding how multicellular and tissue-level Ca²⁺ signals are generated physiologically, and disrupted in pathological states opens new avenues for therapeutic interventions.

The goal of this Research Topic is to present a current and comprehensive collection of research showcasing the state of the art with respect to the acquisition, analysis, and interpretation of intercellular Ca²⁺ signal dynamics at the tissue and organ level.

The Research Topic invites contributions that focus on, but are not limited to, the following themes:
• Biological Developments: Novel data that advances our knowledge of intercellular Ca²⁺ signal propagation and function in tissues or whole organisms;
• Imaging Advances: Contributions that showcase imaging techniques, such as super-resolution microscopy or multiphoton microscopy, that can capture the complexity of Ca²⁺ dynamics in tissue models;
• Technological Innovations: Contributions that highlight novel imaging tools and molecular probes to detect or manipulate Ca²⁺ signaling allowing for a deeper understanding of intercellular communication;
• Data Analysis Innovations: Contributions that address challenges in data processing and analysis, particularly in handling large and complex datasets generated from multicellular imaging studies;
• Interdisciplinary Approaches: Studies that combine experimental biology and mathematical modeling to enhance our understanding of Ca²⁺ signal propagation at the multicellular level;
• Pathophysiological Insights: Studies that inform the mechanisms that link pathological changes in Ca²⁺ signal propagation at the tissue level to disease etiology.

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Intercellular Calcium Signal Propagation in Tissue Function