Loose Coupling between the Voltage Sensor and the Activation Gate in Mammalian HCN Channels Suggests a Gating Mechanism

Wu, X, Cunningham, K.P., Bruening-Wright, A, Pandey, S and Larsson, H. P. 2024. Loose Coupling between the Voltage Sensor and the Activation Gate in Mammalian HCN Channels Suggests a Gating Mechanism. International Journal of Molecular Sciences. 25 (8) 4309. https://doi.org/10.3390/ijms25084309

TitleLoose Coupling between the Voltage Sensor and the Activation Gate in Mammalian HCN Channels Suggests a Gating Mechanism
TypeJournal article
AuthorsWu, X, Cunningham, K.P., Bruening-Wright, A, Pandey, S and Larsson, H. P.
Abstract

Voltage-gated potassium (Kv) channels and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels share similar structures but have opposite gating polarity. Kv channels have a strong coupling (>109) between the voltage sensor (S4) and the activation gate: when S4s are activated, the gate is open to >80% but, when S4s are deactivated, the gate is open <10−9 of the time. Using noise analysis, we show that the coupling between S4 and the gate is <200 in HCN channels. In addition, using voltage clamp fluorometry, locking the gate open in a Kv channel drastically altered the energetics of S4 movement. In contrast, locking the gate open or decreasing the coupling between S4 and the gate in HCN channels had only minor effects on the energetics of S4 movement, consistent with a weak coupling between S4 and the gate. We propose that this loose coupling is a prerequisite for the reversed voltage gating in HCN channels.

KeywordsHCN channels
Kv channels
voltage clamp fluorometry
voltage gating
electromechanical coupling
Article number4309
JournalInternational Journal of Molecular Sciences
Journal citation25 (8)
ISSN1422-0067
Year2024
PublisherMDPI
Publisher's version
License
CC BY 4.0
File Access Level
Open (open metadata and files)
Digital Object Identifier (DOI)https://doi.org/10.3390/ijms25084309
Web address (URL)https://www.mdpi.com/1422-0067/25/8/4309
Publication dates
Published13 Apr 2024
Supplemental file
File Access Level
Open (open metadata and files)

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