DIHYDROPYRIDINE ACTION ON VOLTAGE-DEPENDENT POTASSIUM CHANNELS EXPRESSED IN XENOPUS OOCYTES

Dihydropyridines (DHPs) are well known for their effects on L-type vol tage-dependent Ca2+ channels. However, these drugs also affect other v oltage-dependent ion channels, including Shaker K+ channels. We examin ed the effects of DHPs on the Shaker K+ channels expressed in Xenopus oocytes. Intracellular applications of DHPs quickly and reversibly ind uced apparent inactivation in the Shaker K+ mutant channels with disru pted 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 molecule s to the channel is consistent with the results obtained in our experi ments.