Mutation in pore domain uncovers cation- and voltage-sensitive recovery from inactivation in KAT1 channel

Moroni, A and Gazzarrini, S and Cerana, R and Colombo, R and Sutter, J U and DiFrancesco, D and Gradmann, D and Thiel, G (2000) Mutation in pore domain uncovers cation- and voltage-sensitive recovery from inactivation in KAT1 channel. Biophysical Journal, 78 (4). pp. 1862-1871. ISSN 0006-3495 (https://doi.org/10.1016/S0006-3495(00)76735-X)

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Abstract

Effects of threonine substitution by glutamine at position 256 in the pore of the KAT1 channel have been investigated by voltage-clamp, using heterologous gene expression in Xenopus oocytes. The major discrepancy in T256Q from the wild-type channel (wt) was cation specific. While K(+) currents were reduced in a largely scalar fashion, the NH(4)(+) current exhibited slow, voltage-dependent inhibition during hyperpolarization. The same effects could be induced in wt, or intensified in T256Q, by addition of the impermeant cation methylammonium (MA(+)) to the bath. This stresses that both the mutation and MA(+) affect a mechanism already present in the wt. Assuming that current inhibition could be described as entry of the channel into an inactive state, we modeled in both wt and in T256Q the relaxation kinetics of the clamp currents by a C-O-I gating scheme, where C (closed) and I (inactivated) are nonconductive states, and O is an open state allowing K(+) and NH(4)(+) passage. The key reaction is the transition I-O. This cation-sensitive transition step ensures release of the channel from the inactive state and is approximately 30 times smaller in T256Q compared to wt. It can be inhibited by external MA(+) and is stimulated strongly by K(+) and weakly by NH(4)(+). This sensitivity of gating to external cations may prevent K(+) leakage from cation-starved cells.

  • Item type:Article
    ID code:39689
    Dates:
    Date
    Event
    April 2000
    Published
    Subjects:Science > Physics
    Department:Faculty of Science > Physics
    Depositing user: Pure Administrator
    Date deposited:12 May 2012 10:39
    Last modified:08 Apr 2024 19:55
    URI:https://strathprints.strath.ac.uk/id/eprint/39689
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