P21ras Oncogene Protein Selectively Increases Low‐voltage‐activated Ca2+ Current Density in Embryonic Chick Dorsal Root Ganglion Neurons

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Abstract
P21ras protein resembles the α subunit of trimeric G‐proteins, which regulate ion channel function. We now report a modulation of Ca2+ channels in vertebrate sensory neurons by p21ras in addition to its role in cell growth and differentiation. Quantitative microinjection of oncogenic p21‐H‐ras into embryonic chick dorsal root ganglion neurons was performed. After 4 h the current density of the low‐voltage‐activated (LVA; T‐type) Ca2+ channels was increased. However, in contrast to trimeric G‐proteins, which inhibit high‐voltage‐activated (HVA) Ca2+ channels in chick dorsal root ganglion neurons, p21ras did not significantly affect HVA Ca2+ currents. To study the time course of p21ras action, guanosine triphosphate‐preloaded p21ras was added to the patch pipette. Full‐length ras was effective only after a delay of 20 ‐30 min. C‐terminal modification by cellular enzymes is required to activate full‐length ras, and can account for the observed delay. Unexpectedly, C‐terminal‐truncated p2lras, which was found to be inactive in biological assays, enhanced LVA Ca2+ currents within minutes. This suggests a G‐protein‐like modulation of the LVA Ca2+ channel by p21ras. In an early phase of neuronal differentiation, dorsal root ganglion neurons express only LVA Ca2+ currents. The regulatory role of p21ras on LVA channels may therefore be particularly important during differentiation.