NCS-1 differentially regulates growth cone and somata calcium channels in Lymnaea neurons

Local voltage-gated calcium channels, which regulate intracellular Ca²⁺ levels by allowing Ca²⁺ influx, play an important role in guiding and shaping growth cones, and in regulating the outgrowth and branching of neurites. Therefore, elucidating the mechanisms that regulate the biophysical properties of whole-cell calcium currents in the growth cones and somata of growing neurons is important to improving our understanding of neuronal development and regeneration. In this study, taking advantage of the large size of the pedal A (PeA) neurons in Lymnaea stagnalis , we compared the biophysical properties of somata and growth cone whole-cell calcium channel currents using Ba²⁺ and Ca²⁺ as current carriers. We found that somata and growth cone currents exhibit similar high-voltage activation properties. However, Ba²⁺ and Ca²⁺ currents in growth cones and somata are differentially affected by a dominant-negative peptide containing the C-terminal amino acid sequence of neuronal calcium sensor-1 (NCS-1). The peptide selectively reduces the peak and sustained components of current densities and the slope conductance in growth cones, and shifts the reversal potential of the growth cone currents to more hyperpolarized voltages. In contrast, the peptide had no significant effect on the somata calcium channels. Thus, we conclude that NCS-1 differentially modulates Ca²⁺ currents in the somata and growth cones of regenerating neurons, and may serve as a key regulator to facilitate the growth cone calcium channel activity.