Long-term exposure to retinoic acid induces the expression of IRK1 channels in HERG channel-endowed neuroblastoma cells.
The modulation of inward K+ conductances was studied during neuronal differentiation of human SH-SY5Y neuroblastoma cells. Under standard culture conditions, these cells express the herg gene, and the HERG current is the main inward K+ current regulating their Vrest. After 10-20 days exposure to Retinoic Acid (RA), SH-SY5Y cells showed, in addition to HERG currents, a novel current characterized by inward rectification, dependence on the extracellular K+ concentration, and blockade by Cs+ and Ba2+, the main features of the IRK1 current. The appearance of this current is accompanied by a strong hyperpolarisation of Vrest. RT-PCR experiments confirmed that a transcript of the IRK1 (Kir 2.1) gene actually appears in SH-SY5Y cells treated for 10-20 days with RA. On the whole, data here presented demonstrate that RA-induced neuronal differentiation of neuroblastoma cells is accompanied by the switch from a HERG-driven to a IRK1-driven control of Vrest, similarly to what happens in normal differentiating neurons; however, in tumor cells, this switch does not imply the abolition of HERG channel expression.
Arcangeli
A
A
Institute of General Pathology, University of Florence, Italy.
Rosati
B
B
Cherubini
A
A
Crociani
O
O
Fontana
L
L
Passani
B
B
Wanke
E
E
Olivotto
M
M
D027682:Cation Transport Proteins; D002454:Cell Differentiation; D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D004553:Electric Conductivity; D051638:Ether-A-Go-Go Potassium Channels; D015870:Gene Expression; D006801:Humans; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000096:biosynthesis* / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger / Q000032:analysis; D013997:Time Factors; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D014212:Tretinoin / Q000494:pharmacology*; 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; D024661:Potassium Channels, Inwardly Rectifying; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D014212:Tretinoin