title: Effect of some anticancer drugs on the surface membrane electrical properties of differentiated murine neuroblastoma cells.
abstract: The effect of some anticancer agents that produce toxic effects on electrically excitable cells in vivo was studied in vitro with the use of differentiated N1E-115 murine neuroblastoma cells and single microelectrode electrical recording. In the presence of 10(-7) g/ml tetrodotoxin, following the release of 500-millisecond conditioning hyperpolarization, the cells exhibited Ca2+-dependent action potentials. Local application to N1E-115 neuroblastoma cells of cisplatin (cis-PDD) for 30 seconds from a drug-containing effusion pipette produced a dose-dependent reversible inhibition of the Ca2+-dependent action potential, with a 61% inhibition at 1.7 microM and 67% inhibition at 17 microM cis-PDD. trans-Dichlorodiammineplatinum(II) and platinic(IV) chloride, both of which lacked the growth inhibitory properties of cis-PDD against N1E-115 neuroblastoma cells, at concentrations of 170 and 120 microM produced only an 11 and 19% inhibition of the Ca2+-dependent action potential, respectively. Vincristine at a concentration of 1 microM reversibly inhibited the Ca2+-dependent action potential by 48%. 3'-Deamino-3'-(3''-cyano-4''-morpholinyl)doxorubicin, a more potent experimental antitumor agent than doxorubicin, at 10(-8) M inhibited the Ca2+-dependent action potential by 22%, similar to the inhibition previously reported for doxorubicin. None of the agents affected the cell transmembrane potential, which suggests a lack of an effect on the mechanisms responsible for maintaining the resting cell membrane potential difference. The effects of the agents on the Ca2+-dependent action potential might reflect a direct effect on a plasma membrane Ca2+ channel or on the lipid domain around the channels, or they might be produced by changes in intracellular Ca2+ homeostasis, among other mechanisms. It is not known whether a change in the membrane Ca2+ current is related to the antitumor effects of the agents, but such a change may contribute to the neurotoxicity of cis-PDD and vincristine and the cardiac toxicity of the anthracycline.
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002454:Cell Differentiation; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009447:Neuroblastoma / Q000188:drug therapy* / Q000503:physiopathology; D014750:Vincristine / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D014750:Vincristine; D004317:Doxorubicin; C038555:3'-deamino-3'-(3-cyano-4-morpholinyl)doxorubicin; D002945:Cisplatin; D002118:Calcium