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 we re investigated in this study. Rutaecarpine (2-100 muM) suppressed the ampl itude 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 1 1 muM. I-K(DR) present in these cells is sensitive to the inhibition by qui nidine and dendrotoxin, yet not by E-4031. The presence of rutaecarpine enh anced the rate and extent of I-K(DR), inactivation, although it had no effe ct on the initial activation phase of I-K(DR) Recovery from block by rutaec arpine (5 muM) was fitted by a single exponential with a value of 2.87 s. C rossover of tail currents in the presence of rutaecarpine was also observed . Cell-attached single-channel recordings revealed that rutaecarpine decrea sed channel activity, but it did not after single-Channel amplitude. With t he aid of the binding scheme, a quantitative description of the rutaecarpin e actions on I-K(DR) was provided. However, rutaecarpine (20 muM) had no ef fect on L-type Ca2+ current. Under current-clamp configuration, rutaecarpin e 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) (C) 2001 Elsevier Science Ltd. All rights reser ved.