A HERG‐like K+ channel in rat F‐11 DRG cell line: pharmacological identification and biophysical characterization.

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.