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.

Ca2+ channel; Ca2+ signaling; Dopamine; Inhibitor; Latroeggtoxin-VI; PC12 cell.