Infrared Neural Stimulation Induces Intracellular Ca Release Mediated by Phospholipase C

The influence of infrared laser pulses on intracellular Ca signaling was investigated in neural cell lines with fluorescent live cell imaging. The probe Fluo-4 was used to measure Ca 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 Ca transient with similar dose-response characteristics in hippocampal neurons and glioblastoma cells (half-maximal effective energy density EC of around 58 J.cm ). For both type of cells, the source of the infrared-induced Ca transients was found to originate from intracellular stores and to be mediated by phospholipase C and IP -induced Ca 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/IP cell signaling cascade has many potential applications including the development of optoceutical therapeutics.