Inhibition of Toosendanin on the delayed rectifier potassium current in neuroblastoma x glioma NG108-15 cells.

The effect of Toosendanin (TSN), a presynaptic transmission blocker, on the outward delayed rectifier potassium current (IKD) of NG108-15 cells was studied by using the whole-cell voltage-clamp technique. It was observed that externally applying TSN not only reduced IKD amplitude in a dose-dependent and partial reversible manner but also accelerated its inactivation. The effect of internally applying TSN was also examined by including TSN in the electrode, and it was the same as that of externally applying TSN. Further, comparison observations with TEA, 4-AP, verapamil, nifedipine, and (+/-)-Bay K 8644 were also made, and the results were as follows. The time courses of TSN's inhibition effect as well as its recovery after washing were much slower than those of TEA and 4-AP. Externally applying TEA or 4-AP reduced IKD amplitude but did not accelerate its inactivation. Externally applying verapamil, nifedipine, or (+/-)-Bay K 8644, however, similarly to the effect of TSN, not only reduced IKD amplitude but also accelerated its inactivation. Thus, from the obtained results it is suggested that TSN might diffuse into the cell interior and act intracellularly, and the underlying mechanism might be different from that of TEA and 4-AP but similar to that of verapamil, nifedipine, and (+/-)-Bay K 8644 to some extent.