Rutaecarpine-induced block of delayed rectifier K + current in NG108-15 neuronal cells

• Published in: Neuropharmacology Vol. 41; no. 7; pp. 834 - 843
• Main Authors: Wu, Sheng-Nan, Lo, Yuk-Keung, Chen, Hsinyo, Li, Hui-Fang, Chiang, Hung-Ting
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.12.2001; Elsevier
• Subjects: Action potential; Action Potentials - drug effects; Alkaloids - pharmacology; Animals; Biological and medical sciences; Calcium Channels - metabolism; Delayed rectifier K + current; Delayed Rectifier Potassium Channels; Dose-Response Relationship, Drug; General pharmacology; Indole Alkaloids; Ion Channel Gating - drug effects; Kinetics; Medical sciences; Membrane Potentials - drug effects; Membrane Potentials - physiology; Mice; Neurons - drug effects; Neurons - physiology; NG108-15 cells; Patch-Clamp Techniques; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Potassium Channel Blockers; Potassium Channels - metabolism; Potassium Channels - physiology; Potassium Channels, Voltage-Gated; Quinazolines; Rats; Rutaecarpine; Tumor Cells, Cultured - drug effects; Tumor Cells, Cultured - physiology; Vasodilator Agents - pharmacology; Delayed rectifier K + current; Action potential; NG108-15 cells; Rutaecarpine; Rat; Pharmacognosy; Potassium ion; Rodentia; Central nervous system; Ionic channel; Ionic current; In vitro; Biological activity; Vertebrata; Alkaloid; Mammalia; Calcium ion; Neuron; Mouse; Animal; Established cell line; Plant origin; Brain (vertebrata)
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/S0028-3908(01)00114-9

The effects of rutaecarpine on ionic currents of NG108-15 neuronal cells were investigated in this study. Rutaecarpine (2–100 μM) suppressed the amplitude of delayed rectifier K + current ( I K(DR)) in a concentration-dependent manner. The IC 50 value for rutaecarpine-induced inhibition of I K(DR) was 11 μM. I K(DR) present in these cells is sensitive to the inhibition by quinidine and dendrotoxin, yet not by E-4031. The presence of rutaecarpine enhanced the rate and extent of I K(DR) inactivation, although it had no effect on the initial activation phase of I K(DR). Recovery from block by rutaecarpine (5 μM) was fitted by a single exponential with a value of 2.87 s. Crossover of tail currents in the presence of rutaecarpine was also observed. Cell-attached single-channel recordings revealed that rutaecarpine decreased channel activity, but it did not alter single-channel amplitude. With the aid of the binding scheme, a quantitative description of the rutaecarpine actions on I K(DR) was provided. However, rutaecarpine (20 μM) had no effect on L-type Ca 2+ current. Under current-clamp configuration, rutaecarpine prolonged action potential duration in NG108-15 cells. These results show that rutaecarpine is a blocker of the K DR channel. The increase in action potential duration induced by rutaecarpine can be explained mainly by its blocking actions on I K(DR).