Infrared neural stimulation induces intracellular Ca²⁺ release mediated by phospholipase C

The influence of infrared laser pulses on intracellular Ca²⁺ signaling was investigated in neural cell lines with fluorescent live cell imaging. The probe Fluo-4 was used to measure Ca²⁺ in HT22 mouse hippocampal neurons and nonelectrically excitable U87 human glioblastoma cells exposed to 50 to 500 ms infrared pulses at 1470 nm. Fluorescence recordings of Fluo-4 demonstrated that infrared stimulation induced an instantaneous intracellular Ca²⁺ transient with similar dose-response characteristics in hippocampal neurons and glioblastoma cells (half-maximal effective energy density EC₅₀ of around 58 J.cm^-2 ). For both type of cells, the source of the infrared-induced Ca²⁺ transients was found to originate from intracellular stores and to be mediated by phospholipase C and IP₃ -induced Ca²⁺ release from the endoplasmic reticulum. The activation of phosphoinositide signaling by IR light is a new mechanism of interaction relevant to infrared neural stimulation that will also be widely applicable to nonexcitable cell types. The prospect of infrared optostimulation of the PLC/IP₃ cell signaling cascade has many potential applications including the development of optoceutical therapeutics.