Alamethicin channel inactivation caused by voltage-driven flux of alamethicin.

Autor: Maraj JJ; Department of Mechanical Aerospace and Biomedical Engineering, University of Tennessee, Knoxville, TN 37996, USA., Ringley JD; Department of Mechanical Aerospace and Biomedical Engineering, University of Tennessee, Knoxville, TN 37996, USA., Sarles SA; Department of Mechanical Aerospace and Biomedical Engineering, University of Tennessee, Knoxville, TN 37996, USA. Electronic address: ssarles@utk.edu.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Biomembranes [Biochim Biophys Acta Biomembr] 2024 Dec; Vol. 1866 (8), pp. 184386. Date of Electronic Publication: 2024 Sep 27.
DOI: 10.1016/j.bbamem.2024.184386
Abstrakt: We show that voltage alone can inactivate alamethicin channels, which has been previously observed for monazomycin and suzukacillin channels. The voltage required to trigger inactivation is above the potential to form channels, and, like with channel activation, this threshold reduces with increasing peptide concentration and membrane fluidity. Since similar monazomycin channels inactivate via channel break up and translocation, we hypothesized that inactivation of alamethicin channels occurs via the same mechanism. Our data prove this hypothesis to be true through two experiments. First, we show that inactivation of channels at positive voltages when peptides are supplied to only the cis side correlates to new channel activity on the trans side at negative potentials. This result indicates translocation of alamethicin peptides occurs only during voltage-induced inactivation. Second, we measured the ratio of steady-state (with inactivation) to ideal (without inactivation) conductance versus voltage for membranes with equal amounts of alamethicin on both sides and used these values to quantify alamethicin flux. Plotting flux versus steady-state conductance across multiple alamethicin concentrations shows a single linear dependence, signifying that translocated peptides originate from active channels that break up under prolonged voltage. Given the frequent use of alamethicin as model ion channels, these results add important understanding of their kinetic responses when subjected to prolonged, high voltages.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Stephen A Sarles reports financial support was provided by The University of Tennessee Knoxville. Stephen A. Sarles reports financial support was provided by Air Force Office of Scientific Research. Joshua J. Maraj reports financial support was provided by Air Force Office of Scientific Research. Jessie D. Ringley reports financial support was provided by Air Force Office of Scientific Research. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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