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 d ifferentiation of human SH-SY5Y neuroblastoma cells. Under standard cu lture conditions, these cells express the herg gene, and the HERG curr ent is the main inward K+ current regulating their V-rest. After 10-20 days exposure to Retinoic Acid (RA), SH-SY5Y cells showed, in additio n to HERG: currents, a novel current characterized by inward rectifica tion, dependence on the extracellular K+ concentration, and blockade b y Cs+ and Ba2+, 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 neuron al differentiation of neuroblastoma cells is accompanied by the switch from a HERG-driven to a IRK1-driven control of V-rest, similarly to w hat happens in normal differentiating neurons; however, in tumor cells , this switch does not imply the abolition of HERG channel expression. (C) 1998 Academic Press.