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.
Department of General Physiology and Biochemistry, University of Milano, Italy.
L
L
Faravelli
A
A
Arcangeli
M
M
Olivotto
E
E
Wanke
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001932:Brain Neoplasms / Q000378:metabolism; D027682:Cation Transport Proteins; D002413:Cations, Divalent / Q000494:pharmacology; D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D004594:Electrophysiology; D051638:Ether-A-Go-Go Potassium Channels; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D006822:Hybrid Cells; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D009447:Neuroblastoma / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D013424:Sulfanilamides / Q000494:pharmacology; D015534:Trans-Activators; D000096926:Benzenesulfonamides
D000889:Anti-Arrhythmia Agents; D001562:Benzimidazoles; D027682:Cation Transport Proteins; D002413:Cations, Divalent; D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D010880:Piperidines; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011725:Pyridines; D013424:Sulfanilamides; D015534:Trans-Activators; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; C063968:E 4031; C073190:WAY 123398; D000096926:Benzenesulfonamides