Sensing intra- and extra-cellular Ca²⁺ in the islet of Langerhans

Calcium ions (Ca²⁺) take part in intra- and inter-cellular signaling to mediate cellular functions. Sensing this ubiquitous messenger is instrumental in disentangling the specific functions of cellular sub-compartments and/or intercellular communications. In this review, the authors first describe intra- and inter-cellular Ca²⁺ signaling in relation to insulin secretion from the pancreatic islets, and then outline the development of diverse sensors, for example, chemically synthesized indicators, genetically encoded proteins, and ion-selective microelectrodes, for intra- and extra-cellular sensing of Ca²⁺. Particular emphasis is placed on emerging approaches in this field, such as low-affinity Ca²⁺ indicators and unique Ca²⁺-responsive composite materials. The authors conclude by remarking on the challenges and opportunities for further developments in this field, which may facilitate a more comprehensive understanding of Ca²⁺ signaling within and outside the islets, and its relevance in health and disease. Refereed/Peer-reviewed