Abstract
1. The relationships between the K+ inward rectifier current present in neuroblastoma cells (IIR) and the current encoded by the human ether-á-go-go-related gene (HERG), IHERG, and the rapidly activating repolarizing cardiac current IK(r), were investigated in a rat dorsal root ganglion (DRG) x mouse neuroblastoma hybrid cell line (F-11) using pharmacological and biophysical treatments. 2. IIR shared the pharmacological features described for IK(r), including the sensitivity to the antiarrhythmic drugs E4301 and WAY-123,398, whilst responding to Cs+, Ba2+ and La3+ in a similar way to IHERG. 3. The voltage-dependent gating properties of IIR were similar to those of IK(r) and IHERG, although IIR outward currents were negligible in comparison. 4. In high K+ extracellular solutions devoid of divalent cations, IIR deactivation kinetics were removed resulting in long-lasting currents apparently activated in hyperpolarization, with a marked (2.7-fold) increase in conductance, as recorded from the instantaneous linear current-voltage relationship at -120 mV. Re-addition of Ca2+ restored the original closure of the channel whereas re-addition of Mg2+ reduced the peak current. 5. The IIR described here, the heart IK(r) and the IHERG could be successfully predicted by a unique kinetic model where the voltage dependencies of the activation/inactivation gates were properly voltage shifted. On the whole, IIR seems to be the first example of a HERG-type current constitutively expressed and operating in mammalian cells of the neuronal lineage.