Effects of neutral ionophores on membrane electrical characteristics of NG108-15 cells.
The effects of several K(+)-selective neutral ionophores on membrane electrical characteristics of differentiated NG108-15 (neuroblastoma X glioma hybrid) cells were examined. Specifically, alterations in membrane resting potential (V(m)), input resistance (R(in)) and electrically-induced action potential generation were determined upon bath application of enniatin (0.1-10 microg/ml), nonactin (0. 1-10 microM) and valinomycin (0.1-10 microM). Although some cells exhibited a slight hyperpolarization and/or reduced R(in), i.e. membrane electrical correlates of enhanced K(+) loss, neither V(m) nor R(in) were significantly altered by any of the ionophores. However, valinomycin and especially nonactin affected action potentials induced by electrical stimulation. This was apparent in the ablation of action potentials in some cells and in the occurrence of degenerative changes in action potential shape in others. The simultaneous administration of the neutral ionophores and the protonophore CCCP or the superfusion of enniatin, nonactin or valinomycin in high (50 mM) glucose-containing physiological solution did not yield more extensive alterations in V(m) or R(in). These data suggest that the neutral ionophores are unable to materially enhance K(+) flux above the relatively high resting level in NG108-15 cells. Thus, alterations in action potentials appear to be unrelated to K(+) transport activity.
Doebler
J A
JA
Neurotoxicology Branch, Pharmacology Division, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010, USA. jeffrey.doebler@amedd.army.mil
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D047630:Depsipeptides; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005910:Glioma / Q000378:metabolism / Q000648:ultrastructure; D006096:Gramicidin / Q000494:pharmacology; D006822:Hybrid Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D017136:Ion Transport / Q000187:drug effects; D007476:Ionophores / Q000494:pharmacology*; D018942:Macrolides / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D009550:Nigericin / Q000494:pharmacology; D010455:Peptides; D011188:Potassium / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured; D014634:Valinomycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D047630:Depsipeptides; D007476:Ionophores; D018942:Macrolides; D010455:Peptides; C100264:enniatins; D006096:Gramicidin; D014634:Valinomycin; D009550:Nigericin; D011188:Potassium; C050476:nonactin