Fundamentals of Cellular Calcium Signaling: A Primer

Ionized calcium (Ca²⁺) is the most versatile cellular messenger. All cells use Ca²⁺ signals to regulate their activities in response to extrinsic and intrinsic stimuli. Alterations in cellular Ca²⁺ signaling and/or Ca²⁺ homeostasis can subvert physiological processes into driving pathological outcomes. Imaging of living cells over the past decades has demonstrated that Ca²⁺ signals encode information in their frequency, kinetics, amplitude, and spatial extent. These parameters alter depending on the type and intensity of stimulation, and cellular context. Moreover, it is evident that different cell types produce widely varying Ca²⁺ signals, with properties that suit their physiological functions. This primer discusses basic principles and mechanisms underlying cellular Ca²⁺ signaling and Ca²⁺ homeostasis. Consequently, we have cited some historical articles in addition to more recent findings. A brief summary of the core features of cellular Ca²⁺ signaling is provided, with particular focus on Ca²⁺ stores and Ca²⁺ transport across cellular membranes, as well as mechanisms by which Ca²⁺ signals activate downstream effector systems.