Insights into the mediation of Ca signaling in the promoting effects of LETX-VI on the synthesis and release of dopamine.

Latroeggtoxin-VI (LETX-VI) is an active protein and was previously demonstrated to have effects on the synthesis and release of dopamine. Hererin, the involvement of Ca signaling in the effects of LETX-VI on dopamine was systematically investigated, using PC12 cells as a neuron model. LETX-VI was shown to promote dopamine release from PC12 cells both in the presence and absence of extracellular Ca; however the presence of extracellular Ca was favorable for enhancing the promoting effects of LETX-VI on dopamine, because LETX-VI facilitated the influx of extracellular Ca through the L-type calcium channels in plasma membrane (PM) to increase cytosolic Ca concentration. LETX-VI was able to penetrate the PM of PC12 cells to act on the Ca channel proteins IP3Rs and RyRs in the endoplasm reticulum (ER) membrane, opening the Ca channels and promoting the release of ER Ca to elevate cytosolic Ca level. With the help of intracellular Ca chelator BAPTA, the elevated cytosolic Ca level was proven to play crucial role for the enhanced promoting effects of LETX-VI on dopamine. Taken together, LETX-VI is able to open the Ca channels in both PM and ER membrane simultaneously to facilitate extracellular Ca influx and ER Ca release, and thus increases the cytosolic Ca concentration to enhance the promoting effects on the synthesis and release of dopamine.