Long-term modulation of HERG channel gating in hypoxia

Using the patch-clamp technique, we analysed changes in the biophysical pro perties of HERG potassium channels in neuroblastoma cells long-term exposed to hypoxia. In this condition, HERG channels underwent a profound modulati on that consisted of(i) a slowing in open-close kinetics; (ii) a marked hyp erpolarizing shift in voltage dependence of steady-state activation; and (i ii) 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 betwee n -40 and -30 mV. Such a current modulation is suitable to stabilise the re sting potential (V-REST) in hypoxic environments. (C) 2001 Academic Press.