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.
Hui
Kwokyin
K
Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Canada M5S 1A8.
Feng
Zhong-Ping
ZP
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D017952:Ganglia, Invertebrate / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008195:Lymnaea / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009420:Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D051580:Neuronal Calcium-Sensor Proteins / Q000737:chemistry / Q000378:metabolism*; D009479:Neuropeptides / Q000737:chemistry / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
D015220:Calcium Channels; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; D010446:Peptide Fragments; C101464:frequenin calcium sensor proteins