title: Gating charge immobilization caused by the transition between inactivated states in the Kv1.5 channel.
abstract: Sustained Na(+) or Li(+) conductance is a feature of the inactivated state in wild-type (WT) and nonconducting Shaker and Kv1.5 channels, and has been used here to investigate the cause of off-gating charge immobilization in WT and Kv1.5-W472F nonconducting mutant channels. Off-gating immobilization in response to brief pulses in cells perfused with NMG/NMG is the result of a more negative voltage dependence of charge recovery (V(1/2) is -96 mV) compared with on-gating charge movement (V(1/2) is -6.3 mV). This shift is known to be associated with slow inactivation in Shaker channels and the disparity is reduced by 40 mV, or approximately 50% in the presence of 135 mM Cs. Off-gating charge immobilization is voltage-dependent with a V(1/2) of -12 mV, and correlates well with the development of Na(+) conductance on repolarization through C-type inactivated channels (V(1/2) is -11 mV). As well, the time-dependent development of the inward Na(+) tail current and gating charge immobilization after depolarizing pulses of different durations has the same time constant (tau = 2.7 ms). These results indicate that in Kv1.5 channels the transition to a stable C-type inactivated state takes only 2-3 ms and results in strong charge immobilization in the absence of Group IA metal cations, or even in the presence of Na. Inclusion of low concentrations of Cs delays the appearance of Na(+) tail currents in WT channels, prevents transition to inactivated states in Kv1.5-W472F nonconducting mutant channels, and removes charge immobilization. Higher concentrations of Cs are able to modulate the deactivating transition in Kv1.5 channels and prevent the residual slowing of charge return.
authors.affiliation: Department of Physiology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.forename: D
authors.initials: D
authors.lastname: Fedida
mesh_terms: D000200:Action Potentials / Q000502:physiology; D002412:Cations / Q000378:metabolism*; D002586:Cesium / Q000378:metabolism; D004553:Electric Conductivity; D004594:Electrophysiology; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D051666:Kv1.5 Potassium Channel; D008094:Lithium / Q000378:metabolism; D017354:Point Mutation / Q000502:physiology*; D015221:Potassium Channels / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism; D051637:Shaker Superfamily of Potassium Channels; D012964:Sodium / Q000378:metabolism
chemical_list: D002412:Cations; C496981:KCNA5 protein, human; D051666:Kv1.5 Potassium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051637:Shaker Superfamily of Potassium Channels; D002586:Cesium; D008094:Lithium; D012964:Sodium