Voltage gated potassium channels (K_V channels) are important regulators of neuronal and cardiac excitability. In a variety of inherited as well as acquired channelopathies the function of K_V channels is altered leading to life-threatening conditions like cardiac arrhythmias or epilepsy. To prevent or treat such diseases it is necessary to develop compounds which can restore normal channel function. Rottlerin (Mallotoxin) is a naturally occurring modulator of many different molecular processes like inhibition of poteinkinase C or activation of hERG- and BK-channels. Here, we investigated the effect of Rottlerin on several members of the K_V channel family using heterologous expression in Xenopus oocytes and two electrode voltage clamps. Rottlerin activates some K_V channels leaving others unaffected. Activation is caused by a shift of the voltage-dependence of channel activating to more negative potentials. Finally, we have started to gain deeper insights into the molecular mechanisms underlying the activation of K_V family channels by Rottlerin using 3D-homology modeling techniques.