Riluzole inhibits spontaneous Ca 2+ signaling in neuroendocrine cells by activation of K + channels and inhibition of Na + channels

The neuroprotective drug riluzole has multiple effects on cellular signaling. We found that riluzole rapidly and reversibly inhibited spontaneous Ca 2+ oscillations in both immortalized GnRH‐secreting hypothalamic neurons (GT1 cells) and in the prolactin and growth‐hormone‐secreting GH 3 cell line. At lower concentrations (100 n M –5 μ M ), riluzole reduced the amplitude and frequency of spontaneous Ca 2+ oscillations, whereas at higher concentrations it abolished spontaneous Ca 2+ signaling. Whole‐cell current clamp recordings in GH 3 cells revealed that riluzole decreased the action potential frequency, amplitude, and duration. Riluzole inhibited voltage‐gated Na + currents, increased iberiotoxin‐sensitive voltage‐gated K + currents, and had no effect on voltage‐gated Ca 2+ currents in GH 3 cells. Riluzole also inhibited voltage‐gated Na + currents and increased voltage‐gated K + channels in GT1 cells. The inhibitory effects of riluzole on Ca 2+ signaling were blocked by pretreatment with iberiotoxin in GH 3 cells, but only partially reduced by iberiotoxin in GT1 cells. These results indicate that riluzole inhibits Ca 2+ signaling primarily by activation of K + channels in GH 3 cells, and also by inhibition of Na + channels in GT1 cells. Riluzole's inhibition of spontaneous excitability and Ca 2+ signaling may be involved in its multiple effects on cellular function in the nervous system.British Journal of Pharmacology (2003) 140 , 881–888. doi: 10.1038/sj.bjp.0705491