Distal C terminus of Ca_V1.2 channels plays a crucial role in the neural differentiation of dental pulp stem cells

L-type voltage-dependent Ca_V1.2 channels play an important role in the maintenance of intracellular calcium homeostasis, and influence multiple cellular processes. C-terminal cleavage of Ca_V1.2 channels was reported in several types of excitable cells, but its expression and possible roles in non-excitable cells is still not clear. The aim of this study was to determine whether distal C-terminal fragment of Ca_V1.2 channels is present in rat dental pulp stem cells and its possible role in the neural differentiation of rat dental pulp stem cells. We generated stable Ca _V1.2 knockdown cells via short hairpin RNA (shRNA). Rat dental pulp stem cells with deleted distal C-terminal of Ca_V1.2 channels lost the potential of differentiation to neural cells. Re-expression of distal C-terminal of Ca_V1.2 rescued the effect of knocking down the endogenous Ca_V1.2 on the neural differentiation of rat dental pulp stem cells, indicating that the distal C-terminal of Ca_V1.2 is required for neural differentiation of rat dental pulp stem cells. These results provide new insights into the role of voltage-gated Ca²⁺ channels in stem cells during differentiation.