Rutaecarpine-induced block of delayed rectifier K+ current in NG108-15 neuronal cells.
The effects of rutaecarpine on ionic currents of NG108-15 neuronal cells were investigated in this study. Rutaecarpine (2-100 microM) suppressed the amplitude of delayed rectifier K+ current (I(K(DR))) in a concentration-dependent manner. The IC50 value for rutaecarpine-induced inhibition of I(K(DR)) was 11 microM. 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 microM) 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 microM) had no effect on L-type Ca2+ 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)).
Wu
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Department of Medical Education and Research, Kaohsiung Veterans General Hospital, 386 Ta-Chung 1st Road, 813, Kaohsiung, Taiwan. snwu@isca.vghks.gov.tw
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Chen
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Chiang
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D000200:Action Potentials / Q000187:drug effects; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D051668:Delayed Rectifier Potassium Channels; D004305:Dose-Response Relationship, Drug; D026121:Indole Alkaloids; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D011799:Quinazolines; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology; D052999:Quinazolinones
D000470:Alkaloids; D015220:Calcium Channels; D051668:Delayed Rectifier Potassium Channels; D026121:Indole Alkaloids; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011799:Quinazolines; D014665:Vasodilator Agents; C028632:rutecarpine; D052999:Quinazolinones