Ras proteins activate calcium channels in neuronal cells.
Ras (p21) proteins are involved in the control of cell growth and differentiation, but the mechanism by which they exert these effects is not yet known. Here we present evidence that c-Ha-ras (p21(Gly-12)) and its oncogenic mutant T24-ras (p21(Val-12)) selectively induce omega-conotoxin and dihydropyridine-sensitive Ca2+ currents within a few hours after introduction into the cytoplasm of neuroblastoma x glioma hybrid cells. Whereas control cells exhibited a mean Ca2+ current of 250 pA, it amounted to 730 pA in cells pretreated with ras protein. In cells loaded with p21(Gly-12), the effect occurred after 2 hours and was terminated after 8 hours. In contrast, introduction of p21(Val-12) resulted in a prolonged delay (6 hours) of the effect which lasted for more than 24 hours. When ras proteins were preactivated with the non-hydrolysable GTP analog GppNHp, the time courses of both p21(Gly-12) and p21(Val-12) effects were fast and sustained, suggesting that in intact cells (i) the GDP/GTP exchange is faster for p21(Gly-12) compared to p21(Val-12) and (ii) inactivation of p21(Gly-12) is mediated by GAP-induced GTPase activity. T-type Ca2+ currents and K+ currents were unaffected by ras proteins.
Hescheler
J
J
Pharmakologisches Institut der Freien Universität Berlin, Germany.
Klinz
F J
FJ
Schultz
G
G
Wittinghofer
A
A
D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D004095:Dihydropyridines / Q000494:pharmacology; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000502:physiology; D006822:Hybrid Cells / Q000187:drug effects; D008845:Microinjections / Q000379:methods; D008978:Mollusk Venoms / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D015689:Oncogene Protein p21(ras) / Q000494:pharmacology*; D015513:Oncogene Proteins / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
D015220:Calcium Channels; D004095:Dihydropyridines; D008978:Mollusk Venoms; D015513:Oncogene Proteins; D011994:Recombinant Proteins; D020866:omega-Conotoxin GVIA; D019204:GTP-Binding Proteins; D015689:Oncogene Protein p21(ras)