A high-Na(+) conduction state during recovery from inactivation in the K(+) channel Kv1.5.
Na(+) conductance through cloned K(+) channels has previously allowed characterization of inactivation and K(+) binding within the pore, and here we have used Na(+) permeation to study recovery from C-type inactivation in human Kv1.5 channels. Replacing K(+) in the solutions with Na(+) allows complete Kv1.5 inactivation and alters the recovery. The inactivated state is nonconducting for K(+) but has a Na(+) conductance of 13% of the open state. During recovery, inactivated channels progress to a higher Na(+) conductance state (R) in a voltage-dependent manner before deactivating to closed-inactivated states. Channels finally recover from inactivation in the closed configuration. In the R state channels can be reactivated and exhibit supernormal Na(+) currents with a slow biexponential inactivation. Results suggest two pathways for entry to the inactivated state and a pore conformation, perhaps with a higher Na(+) affinity than the open state. The rate of recovery from inactivation is modulated by Na(+)(o) such that 135 mM Na(+)(o) promotes the recovery to normal closed, rather than closed-inactivated states. A kinetic model of recovery that assumes a highly Na(+)-permeable state and deactivation to closed-inactivated and normal closed states at negative voltages can account for the results. Thus these data offer insight into how Kv1. 5 channels recover their resting conformation after inactivation and how ionic conditions can modify recovery rates and pathways.
Wang
Z
Z
Department of Physiology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
Hesketh
J C
JC
Fedida
D
D
D055592:Biophysical Phenomena; D001703:Biophysics; D002460:Cell Line; D006801:Humans; D017136:Ion Transport; D007700:Kinetics; D051666:Kv1.5 Potassium Channel; D008564:Membrane Potentials; D008954:Models, Biological; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*
C496981:KCNA5 protein, human; D051666:Kv1.5 Potassium Channel; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011994:Recombinant Proteins; D012964:Sodium