Dual mechanisms contribute to enhanced voltage dependence of an electric fish potassium channel.

Autor: Todorovic J; Department of Neuroscience, The University of Texas, Austin, Texas., Swapna I; Department of Neuroscience, The University of Texas, Austin, Texas., Suma A; Institute for Computational Molecular Science, College of Science and Technology & Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, Pennsylvania., Carnevale V; Institute for Computational Molecular Science, College of Science and Technology & Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, Pennsylvania., Zakon H; Department of Neuroscience, The University of Texas, Austin, Texas; Department of Integrative Biology, The University of Texas, Austin, Texas. Electronic address: h.zakon@austin.utexas.edu.
Jazyk: angličtina
Zdroj: Biophysical journal [Biophys J] 2024 Jul 16; Vol. 123 (14), pp. 2097-2109. Date of Electronic Publication: 2024 Mar 01.
DOI: 10.1016/j.bpj.2024.02.028
Abstrakt: The voltage dependence of different voltage-gated potassium channels, described by the voltage at which half of the channels are open (V 1/2 ), varies over a range of 80 mV and is influenced by factors such as the number of positive gating charges and the identity of the hydrophobic amino acids in the channel's voltage sensor (S4). Here we explore by experimental manipulations and molecular dynamics simulation the contributions of two derived features of an electric fish potassium channel (Kv1.7a) that is among the most voltage-sensitive Shaker family potassium channels known. These are a patch of four contiguous negatively charged glutamates in the S3-S4 extracellular loop and a glutamate in the S3b helix. We find that these negative charges affect V 1/2 by separate, complementary mechanisms. In the closed state, the S3-S4 linker negative patch reduces the membrane surface charge biasing the channel to enter the open state while, upon opening, the negative amino acid in the S3b helix faces the second (R2) gating charge of the voltage sensor electrostatically biasing the channel to remain in the open state. This work highlights two evolutionary novelties that illustrate the potential influence of negatively charged amino acids in extracellular loops and adjacent helices to voltage dependence.
Competing Interests: Declaration of interests None of the authors have any interests to declare.
(Copyright © 2024 Biophysical Society. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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