Intracellular Ca2+ concentration ([Ca2+]i) serves as a versatile signal to mediate a remarkable array of cellular processes, including neurotransmitter and hormone secretion, muscle contraction, and gene regulation. To fulfill such diverse functions, cells evolve many strategies to generate Ca2+ signals tailored to specific cellular functions (Berridge et al., 2003). One such strategy is to organize Ca2+-permeable channels and their targets in proximity, forming so-called Ca2+ nano- and microdomains, such that Ca2+ only activates the targets within the domain. Because of the closeness between the Ca2+ source and its targets, many processes governing global Ca2+ signaling become ineffective in local Ca2+ signaling (Neher, 1998). For example, because Ca2+ diffusion from Ca2+ sources often results in steep gradients in [Ca2+], the distance between Ca2+ sources and targets exerts a critical influence on the efficacy and fidelity of signal transduction, as does the sensitivity of the targets to Ca2+. Although the Ca2+ profile created by local Ca2+ events is understood to a great extent, the spatial relationships between Ca2+ sources and their targets are not determined experimentally in most cases, and the understanding of localized Ca2+ signaling is thus incomplete.
