The neuroprotective K-opioid CI-977 alters glutamate-induced calcium signaling in vitro

The effect of the neuroprotective K opioid agonist CI-977 on glutamate (GLU)-stimulated calcium signaling was studied in individual primary rat cortical neurons. Using laser scanning confocal microscopy and the fluorescent calcium probe fluo-3, both the sustained and biphasic intracellular calcium concentration [Ca]i changes induced by GLU (20–40 μUM) were altered by CI-977 (25–100 nM), thereby shifting the neuronal population response from unbuffered to buffered patterns of [Ca]i flux. This effect was consistent with the previously demonstrated neuroprotective action of CI-977 against glutamate toxicity in vitro. The effect of CI-977 in altering GLU-induced [Ca]i signaling was attenuated by naloxone, consistent with a neuroprotective action of CI-977 at opioid receptors, presumably of the k subtype.