title: Separation of M-like current and ERG current in NG108-15 cells.
abstract: Differentiated NG108-15 neuroblastoma x glioma hybrid cells were whole-cell voltage-clamped. Hyperpolarizing pulses, superimposed on a depolarized holding potential (-30 or -20 mV), elicited deactivation currents which consisted of two components, distinguishable by fitting with two exponential functions. Linopirdine [DuP 996, 3,3-bis(4-pyridinylmethyl)-1-phenylindolin-2-one), a neurotransmitter-release enhancer known as potent and selective blocker of the M-current of rat sympathetic neurons, in concentrations of 5 or 10 microM selectively inhibited the fast component (IC50 = 14.7 microM). The slow component was less sensitive to linopirdine (IC50>20 microM). The class III antiarrhythmics [(4-methylsulphonyl)amido]benzenesulphonamide (WAY-123.398) and 1-[2-(6-methyl-2-pyrydinil)ethyl]-4-(4-methylsulphonylaminobenz oyl) piperidine (E-4031), selective inhibitors of the inwardly rectifying ERG (ether-à-go-go-related gene) potassium channel, inhibited predominantly the slow component (IC50 = 38 nM for E-4031). The time constant of the WAY-123.398-sensitive current resembled the time constant of the slow component in size and voltage dependence. Inwardly rectifying ERG currents, recorded in K+ -rich bath at strongly negative pulse potentials, resembled the slow component of the deactivation current in their low sensitivity to linopirdine (28% inhibition at 50 microM). The size of the slow component varied greatly between cells. Accordingly, varied the effect of WAY-123.398 on deactivation current and holding current. RNA transcripts for the following members of the ether-à-go-go gene (EAG) K+ channel family were found in differentiated NG108-15 cells: ERG1, ERG2, EAGI, EAG-like (ELK)1, ELK2; ERG3 was only present in non-differentiated cells. In addition, RNA transcripts for KCNQ2 and KCNQ3 were found in differentiated and non-differentiated cells. We conclude that the fast component of the deactivation current is M-like current and the slow component is deactivating ERG current. The molecular correlates are probably KCNQ2/KCNQ3 and ERG1/ERG2, respectively.
authors.affiliation: Physiologisches Institut, Universität des Saarlandes, Homburg-Saar, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Meves
authors.forename: J R
authors.initials: JR
authors.lastname: Schwarz
authors.forename: I
authors.initials: I
authors.lastname: Wulfsen
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D027682:Cation Transport Proteins; D051638:Ether-A-Go-Go Potassium Channels; D007211:Indoles / Q000494:pharmacology; D051658:KCNQ2 Potassium Channel; D051659:KCNQ3 Potassium Channel; D026901:Membrane Transport Proteins; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D013424:Sulfanilamides / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000502:physiology*; D014407:Tumor Cells, Cultured; D000096926:Benzenesulfonamides
chemical_list: D001562:Benzimidazoles; D001920:Bradykinin; D027682:Cation Transport Proteins; D051638:Ether-A-Go-Go Potassium Channels; D007211:Indoles; D051658:KCNQ2 Potassium Channel; D051659:KCNQ3 Potassium Channel; D026901:Membrane Transport Proteins; D010880:Piperidines; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011725:Pyridines; D013424:Sulfanilamides; C092509:KCNH6 protein, human; C486376:KCNH7 protein, human; C109500:Kcnh6 protein, rat; C109501:Kcnh7 protein, rat; C496915:Kcnq2 protein, rat; C496917:Kcnq3 protein, mouse; C496918:Kcnq3 protein, rat; C063968:E 4031; C073190:WAY 123398; D000096926:Benzenesulfonamides; C061017:linopirdine