Comparative effects of carboxylic ionophores on membrane potential and resistance of NG108-15 cells.
Comparative analyses were conducted to determine the effects of Na(+) (monensin, MON), K(+) (nigericin, NIG) and Ca(2+) (A23187) selective carboxylic ionophores on differentiated NG108-15 (neuroblastoma X glioma hybrid) cells. Alterations in membrane potential (V(m)), input resistance (Rin) and electrically induced action potential generation were measured using intracellular microelectrode techniques in cells treated with 0.1-30 microM MON and NIG and 0.1-10 microM A23187. Responses to the ionophores were similar in that membrane hyperpolarization and unchanged R(in) predominated with all three compounds. However, significant differences between the ionophores were also detected. MON- and A23187-induced hyperpolarization was generally maintained throughout the 24-min superfusion whereas that produced by NIG diminished with time or was replaced by depolarization. In addition, action potential generation was blocked by NIG, whereas MON had no effect and action potential alterations were evident only with the highest A23187 concentration (10 microM). This study represents the initial comprehensive analysis of the effects of carboxylic ionophores on membrane electrical characteristics of an intact cell system and forms the basis for subsequent work using NG108-15 cells as a model system to evaluate potential therapeutic treatments against the carboxylic ionophores.
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
D000001:Calcimycin / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005910:Glioma / Q000473:pathology; D007476:Ionophores / Q000633:toxicity*; D008564:Membrane Potentials / Q000187:drug effects; D008985:Monensin / Q000633:toxicity*; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000187:drug effects*; D009550:Nigericin / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D007476:Ionophores; D000001:Calcimycin; D008985:Monensin; D009550:Nigericin