Fenvalerate-induced Ca2+ transients via both intracellular and extracellular way in mouse GC-2spd (ts) cells

Fenvalerate (Fen) is a widely used synthetic pyrethroid insecticide which is considered to impede the male reproductive function. However, little is known about its underlying mechanism. In this study, we found that fenvalerate affected the Ca(2+) homeostasis, inducing Ca(2+) transients via both intracellular Ca(2+) release and extracellular Ca(2+) influx. Ca(2+) influx was via store-operated channel (SOC). Therefore, the effects of fenvalerate on Ryanodine receptors (RyRs) and Inositol (1,4,5)-trisphosphate receptors (IP(3)Rs) which involved in forming Ca(2+) transient was assessed by pharmacological way. We also demonstrated that fenvalerate affected the expression of both receptors and hindered cell proliferation as well. In addition, we discovered that 2-APB, an antagonist of IP(3)Rs, inhibited GC-2spd (ts) cells (GC-2 cells) proliferation. Cell cycle analysis of GC-2 cells treated with fenvalerate and 2-APB indicated that both of which showed a slight S-phase accumulation. In conclusion, our results demonstrate that fenvalerate-induced Ca(2+) transients from both calcium release through RyRs or IP(3)Rs and calcium influx via SOC. IP(3)Rs seem to serve a predominant role in triggering Ca(2+) transients which could participate to the regulation of GC-2 cell proliferation.