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 (IK(DR)) in a concentration-dependent manner. The IC50 value for rutaecarpine-induced inhibition of IK(DR) was 11 μM. IK(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 IK(DR) inactivation, although it had no effect on the initial activation phase of IK(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 IK(DR) was provided. However, rutaecarpine (20 μM) 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 KDR channel. The increase in action potential duration induced by rutaecarpine can be explained mainly by its blocking actions on IK(DR).
All Science Journal Classification (ASJC) codes
- Cellular and Molecular Neuroscience