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 V(rest). 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 Ba 2+, the main features of the IRK1 current. The appearance of this current is accompanied by a strong hyperpolarisation of V(rest). 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 V(rest), similarly to what happens in normal differentiating neurons; however, in tumor cells, this switch does not imply the abolition of HERG; channel expression.