Dihydropyridine Action on Voltage-dependent Potassium Channels Expressed in Xenopus Oocytes

Dihydropyridines (DHPs) are well known for their effects on L-type voltage-dependent Ca²⁺ channels. However, these drugs also affect other voltage-dependent ion channels, including Shaker K⁺ channels. We examined the effects of DHPs on the Shaker K⁺ channels expressed in Xenopus oocytes. Intracellular applications of DHPs quickly and reversibly induced apparent inactivation in the Shaker K⁺ mutant channels with disrupted N- and C-type inactivation. We found that DHPs interact with the open state of the channel as evidenced by the decreased mean open time. The DHPs effects are voltage-dependent, becoming more effective with hyperpolarization. A model which involves binding of two DHP molecules to the channel is consistent with the results obtained in our experiments.