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Title: Dual mechanisms contribute to enhanced voltage dependence of an electric fish potassium channel
The voltage dependence of different voltage-gated potassium channels, described by the voltage at which half of the channels are open (V1/2), 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 V1/2 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.  more » « less
Award ID(s):
1856695
PAR ID:
10661328
Author(s) / Creator(s):
; ; ; ;
Publisher / Repository:
Cell Press
Date Published:
Journal Name:
Biophysical Journal
Volume:
123
Issue:
14
ISSN:
0006-3495
Page Range / eLocation ID:
2097 to 2109
Subject(s) / Keyword(s):
voltage-gated potassium channel electric fish mormyrid electric organ evolution
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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