title: Profound differences in potassium current properties of normal and Rous sarcoma virus-transformed chicken embryo fibroblasts.
abstract: The membrane currents of chicken embryo fibroblasts (CEFs) transformed by Rous sarcoma virus (RSV) were compared with the currents of their nontransformed counterparts by using the whole-cell patch-clamp technique. In nontransformed CEFs, the main membrane current is a delayed outward K+ current that is sensitive to tetraethylammonium ion but insensitive to 4-aminopyridine. This K+ current is almost independent of the intracellular Ca2+ concentration and becomes completely inactivated at positive membrane potentials with a time constant of about 10 s at +30 mV. In contrast, transformed CEFs exhibit a noninactivating K+ current that strongly depends on the intracellular Ca2+ concentration. This Ca(2+)-dependent K+ current is blocked by the scorpion toxin charybdotoxin with an IC50 value of 19 nM, whereas the K+ current of normal CEFs is insensitive to charybdotoxin (up to 300 nM). The K+ current properties of transformed CEFs were also found after microinjection of purified, enzymatically active pp60v-src into normal CEFs but not after infection of CEFs with the Rous-associated virus RAV5, which lacks the v-src oncogene. Our results suggest that the oncogene product pp60v-src modulates existing K+ channel proteins, leading to profound electrophysiological and pharmacological alterations of the K+ current properties in RSV-transformed CEFs. Furthermore, our experiments identify for the first time K+ channels as possible substrates of pp60v-src.
authors.affiliation: Rudolf-Buchheim-Institut für Pharmakologie, Justus-Liebig-Universität Giessen, Federal Republic of Germany.
authors.forename: H
authors.initials: H
authors.lastname: Repp
authors.forename: H
authors.initials: H
authors.lastname: Draheim
authors.forename: J
authors.initials: J
authors.lastname: Ruland
authors.forename: G
authors.initials: G
authors.lastname: Seidel
authors.forename: J
authors.initials: J
authors.lastname: Beise
authors.forename: P
authors.initials: P
authors.lastname: Presek
authors.forename: F
authors.initials: F
authors.lastname: Dreyer
mesh_terms: D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001358:Avian Sarcoma Viruses / Q000235:genetics*; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D018999:Charybdotoxin; D002642:Chick Embryo; D004546:Elapid Venoms / Q000494:pharmacology; D005347:Fibroblasts / Q000502:physiology; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D008845:Microinjections; D015688:Oncogene Protein pp60(v-src) / Q000008:administration & dosage / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D012604:Scorpion Venoms / Q000494:pharmacology
chemical_list: D004546:Elapid Venoms; D015221:Potassium Channels; D012604:Scorpion Venoms; D018999:Charybdotoxin; D001030:Apamin; C020273:dendrotoxin; D015688:Oncogene Protein pp60(v-src)