Rapid and Targeted Photoactivation of Ca2+ Channels Mediated by Squaraine To Regulate Intracellular and Intercellular Signaling Processes

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.