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Ras proteins activate calcium channels in neuronal cells
J Hescheler1, F J Klinz, G Schultz
1Pharmakologisches Institut der Freien Universität Berlin, Germany.
Cellular Signalling
|January 1, 1991
Summary
Ras proteins regulate cell growth. This study shows Ras proteins selectively induce specific calcium (Ca2+) currents in hybrid cells, with differing time courses for normal and oncogenic forms.
Area of Science:
- Molecular Biology
- Cell Biology
- Neuroscience
Background:
- Ras proteins (p21) are key regulators of cell growth and differentiation.
- The precise mechanisms of Ras protein action remain largely unknown.
Purpose of the Study:
- To investigate the effect of Ras proteins on ion channel activity in neuroblastoma x glioma hybrid cells.
- To elucidate the role of Ras protein isoforms and their activation states in modulating calcium currents.
Main Methods:
- Introduction of c-Ha-ras (p21(Gly-12)) and T24-ras (p21(Val-12)) into hybrid cells.
- Measurement of omega-conotoxin and dihydropyridine-sensitive Ca2+ currents using patch-clamp electrophysiology.
- Preactivation of Ras proteins with GppNHp to assess the role of GTP/GDP exchange.
Main Results:
- Ras proteins selectively induced Ca2+ currents, increasing them from 250 pA to 730 pA.
- p21(Gly-12) induced currents rapidly (2 hours) with short duration (8 hours).
- p21(Val-12) induced currents with a delayed onset (6 hours) and prolonged duration (>24 hours).
- Preactivated Ras proteins showed fast and sustained current induction, indicating differential GDP/GTP exchange and inactivation rates.
Conclusions:
- Ras proteins modulate specific calcium channel activity.
- The kinetics of Ras protein signaling differ between normal and oncogenic forms, influencing downstream effects.
- Ras protein inactivation is likely mediated by GTPase-activating protein (GAP) activity.