A HERG current sustains a cardiac-type action potential in neuroblastoma S cells.
From the adrenergic SH-SY5Y human neuroblastoma clone, we isolated a subclone (21S) endowed with a glial-oriented phenotype. At difference from the parental clone, 21S cells responded to depolarizing stimuli with overshooting action potentials, whose repolarization phase was composed of an initial rapid episode, followed by a long-lasting plateau and a slow return to the resting potential (V(REST)). The action potential depolarization phase was sustained by a TTX-sensitive Na(+) current, while the first repolarizing episode was produced by the scanty delayed rectifier potassium current (I(KDR)) expressed in 21S cells. The bulk of repolarization, including the after-hyperpolarization, was sustained by the human eag related (HERG) potassium current (I(HERG)) that also governs V(REST) in 21S cells. This double role of I(HERG), together with the poor expression of I(KDRs), represents a novel finding in electrophysiology, as well as gives a clue to identify a new excitable element of the complex cellular population of neuroblastoma.
D'Amico
Massimo
M
Department of Experimental Pathology and Oncology, University of Florence, Viale Morgagni 50, Florence 50134, Italy.
Biagiotti
Tiziana
T
Fontana
Lucrezia
L
Restano-Cassulini
Rita
R
Lasagna
Nadia
N
Arcangeli
Annarosa
A
Wanke
Enzo
E
Olivotto
Massimo
M
D015153:Blotting, Western; D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D005455:Fluorescent Antibody Technique; D006321:Heart / Q000502:physiology*; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology / Q000503:physiopathology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D014407:Tumor Cells, Cultured
D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG