Na⁺-Ca²⁺ exchanger mediates ChR2-induced [Ca²⁺]i elevation in astrocytes

Intracellular Ca(2+) elevation resulting from different Ca(2+) pathways may play different roles in astrocyte functions. Channelrhodopsin-2 (ChR2), a light-gated cation channel, has been used to selectively stimulate astrocytes by inducing intracellular Ca(2+) ([Ca(2+)]i) elevation, but the exact underlying mechanism is still unclear. We found that in the absence of extracellular Ca(2+), light stimulation failed to induce [Ca(2+)]i elevation in astrocytes expressed ChR2. Pharmacological experiments excluded the involvement of Ca(2+)-induced Ca(2+) release from intracellular stores. Further experiments demonstrated that the ChR2-induced [Ca(2+)]i elevation was mainly mediated by reversal of the Na(+)-Ca(2+) exchanger following Na(+) influx through ChR2 channels. Since intracellular Na(+) homeostasis plays important roles in astrocytes, including the modulation of [Ca(2+)]i, neurotransmitter uptake and cell metabolism, our results indicate that ChR2 is a good candidate which could be used for mimicking the intracellular Na(+) disturbance in astrocytes that occurs in various physiological and pathological processes including the uptake of neurotransmitters and ischemia, as well as the activities of various cation channels, ion exchangers, and pumps.