Insights into the mediation of Ca2+ 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 Ca²⁺ 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 Ca²⁺; however the presence of extracellular Ca²⁺ was favorable for enhancing the promoting effects of LETX-VI on dopamine, because LETX-VI facilitated the influx of extracellular Ca²⁺ through the L-type calcium channels in plasma membrane (PM) to increase cytosolic Ca²⁺ concentration. LETX-VI was able to penetrate the PM of PC12 cells to act on the Ca²⁺ channel proteins IP3Rs and RyRs in the endoplasm reticulum (ER) membrane, opening the Ca²⁺ channels and promoting the release of ER Ca²⁺ to elevate cytosolic Ca²⁺ level. With the help of intracellular Ca²⁺ chelator BAPTA, the elevated cytosolic Ca²⁺ 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 Ca²⁺ channels in both PM and ER membrane simultaneously to facilitate extracellular Ca²⁺ influx and ER Ca²⁺ release, and thus increases the cytosolic Ca²⁺ concentration to enhance the promoting effects on the synthesis and release of dopamine.