Ryanodine and IP receptor-mediated calcium signaling play a pivotal role in neurological infrared laser modulation.

Pulsed infrared (IR) laser energy has been shown to modulate neurological activity through both stimulation and inhibition of action potentials. While the mechanism(s) behind this phenomenon is (are) not completely understood, certain hypotheses suggest that the rise in temperature from IR exposure could activate temperature- or pressure-sensitive ion channels or create pores in the cellular outer membrane, allowing an influx of typically plasma-membrane-impermeant ions. Studies using fluorescent intensity-based calcium ion ([Formula: see text]) sensitive dyes show changes in [Formula: see text] levels after various IR stimulation parameters, which suggests that [Formula: see text] may originate from the external solution. However, activation of intracellular signaling pathways has also been demonstrated, indicating a more complex mechanism of increasing intracellular [Formula: see text] concentration. We quantified the [Formula: see text] mobilization in terms of influx from the external solution and efflux from intracellular organelles using Fura-2 and a high-speed ratiometric imaging system that rapidly alternates the dye excitation wavelengths. Using nonexcitable Chinese hamster ovarian ([Formula: see text]) cells and neuroblastoma-glioma (NG108) cells, we demonstrate that intracellular [Formula: see text] receptors play an important role in the IR-induced [Formula: see text], with the [Formula: see text] response augmented by ryanodine receptors in excitable cells.