Abstract

As an important cellular signal transduction messenger, Ca2+ has the capability to regulate cell function and control many biochemical processes, including metabolism, gene expression, and cell survival and death. Here, we introduce an accessible method for the photoactivation of Ca2+ channels mediated by squaraine (SQ) to rapidly induce cellular Ca2+ release and activate signal transduction. With a short preparation time, the maximum Ca2+ concentration increase could reach approximately 450% in 30 s, resulting from marked Ca2+ release channel opening in the endoplasmic reticulum (ER). This release was enhanced by another target location of SQ, that is, the outer mitochondrial-associated membrane where Ca2+ channels accumulate, and by the consequent large amounts of reactive oxygen species resulting from the respiratory chain activity stimulated by Ca2+ load. We used this method to investigate cellular signal transduction in different cancer cells and revealed rapid intracellular Ca2+ flow, unidirectional intercellular signaling processes, and neuronal signaling activity, which demonstrated the potential and convenience of the method for routine Ca2+ research.