Long-term modulation of HERG channel gating in hypoxia.
Using the patch-clamp technique, we analysed changes in the biophysical properties of HERG potassium channels in neuroblastoma cells long-term exposed to hypoxia. In this condition, HERG channels underwent a profound modulation that consisted of: (i) a slowing in open-close kinetics; (ii) a marked hyperpolarizing shift in voltage dependence of steady-state activation; and (iii) a slowing of the inactivation removal. The overall physiological impact of these changes in neuroblastoma cells is an increase in the HERG window current in the range of the resting potential (V(REST)), which varied between -40 and -30 mV. Such a current modulation is suitable to stabilise the resting potential (V(REST)) in hypoxic environments.
Fontana
L
L
Department of Experimental Pathology and Oncology, University of Florence, Viale Morgagni 50, Florence, 50134, Italy.
D'Amico
M
M
Crociani
O
O
Biagiotti
T
T
Solazzo
M
M
Rosati
B
B
Arcangeli
A
A
Wanke
E
E
Olivotto
M
M
D027682:Cation Transport Proteins; D002462:Cell Membrane / Q000737:chemistry; D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D006801:Humans; D000860:Hypoxia; D007700:Kinetics; D008564:Membrane Potentials; D009447:Neuroblastoma / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism*; 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