ACTIVATION-DEPENDENT SUBCONDUCTANCE LEVELS IN THE DRK1 K-CHANNEL SUGGEST A SUBUNIT BASIS FOR ION PERMEATION AND GATING

ion permeation and channel opening are two fundamental properties of i on channels, the molecular bases of which are poorly understood. Chann els can exist in two permeability states, open and closed. The relativ e amount of time a channel spends in the open conformation depends on the state of activation. in voltage-gated ion channels, activation inv olves movement of a charged voltage sensor, which is required for chan nel opening. Single-channel recordings of drk1 K channels expressed in Xenopus oocytes suggested that intermediate current levels (sublevels ) may be associated with transitions between the closed and open state s. Because K channels are formed by four identical subunits, each cont ributing to the lining of the pore, it was hypothesized that these sub levels resulted from heteromeric pore conformations. A formal model ba sed on this hypothesis predicted that sublevels should be more frequen tly observed in partially activated channels, in which some but not al l subunits have undergone voltage-dependent conformational changes req uired for channel opening. Experiments using the drk1 K channel, as we ll as drk1 channels with mutations in the pore and in the voltage sens or, showed that the probability of visiting a sublevel correlated with voltage- and time-dependent changes in activation. A subunit basis is proposed for channel opening and permeation in which these processes are coupled.