Mechanism of voltage sensing in Ca2+- and voltage-activated K+ (BK) channels

Willy Carrasquel-Ursulaez; Ignacio Segura; Ignacio Díaz-Franulic; Felipe Echeverría; Yenisleidy Lorenzo-Ceballos; Nicolás Espinoza; Maximiliano Rojas; Jose Antonio Garate; Eduardo Perozo; Osvaldo Alvarez; Fernando D. Gonzalez-Nilo; Ramón Latorre

doi:10.1073/pnas.2204620119

Mechanism of voltage sensing in Ca²⁺- and voltage-activated K⁺ (BK) channels

Willy Carrasquel-Ursulaez, Ignacio Segura, Ignacio Díaz-Franulic, Felipe Echeverría, Yenisleidy Lorenzo-Ceballos, Nicolás Espinoza, Maximiliano Rojas, Jose Antonio Garate, Eduardo Perozo, Osvaldo Alvarez, Fernando D. Gonzalez-Nilo, Ramón Latorre

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

Abstract

In neurosecretion, allosteric communication between voltage sensors and Ca²⁺ binding in BK channels is crucially involved in damping excitatory stimuli. Nevertheless, the voltage-sensing mechanism of BK channels is still under debate. Here, based on gating current measurements, we demonstrate that two arginines in the transmembrane segment S4 (R210 and R213) function as the BK gating charges. Significantly, the energy landscape of the gating particles is electrostatically tuned by a network of salt bridges contained in the voltage sensor domain (VSD). Molecular dynamics simulations and proton transport experiments in the hyperpolarization-activated R210H mutant suggest that the electric field drops off within a narrow septum whose boundaries are defined by the gating charges. Unlike Kv channels, the charge movement in BK appears to be limited to a small displacement of the guanidinium moieties of R210 and R213, without significant movement of the S4.

Original language	English
Article number	e2204620119
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	119
Issue number	25
DOIs	https://doi.org/10.1073/pnas.2204620119
Publication status	Published - 21 Jun 2022

Keywords

allosterism
BK channels
potassium channels
voltage sensitivity

ASJC Scopus subject areas

General

Access to Document

10.1073/pnas.2204620119

Cite this

Carrasquel-Ursulaez, W., Segura, I., Díaz-Franulic, I., Echeverría, F., Lorenzo-Ceballos, Y., Espinoza, N., Rojas, M., Garate, J. A., Perozo, E., Alvarez, O., Gonzalez-Nilo, F. D., & Latorre, R. (2022). Mechanism of voltage sensing in Ca²⁺- and voltage-activated K⁺ (BK) channels. Proceedings of the National Academy of Sciences of the United States of America, 119(25), Article e2204620119. https://doi.org/10.1073/pnas.2204620119

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title = "Mechanism of voltage sensing in Ca2+- and voltage-activated K+ (BK) channels",

abstract = "In neurosecretion, allosteric communication between voltage sensors and Ca2+ binding in BK channels is crucially involved in damping excitatory stimuli. Nevertheless, the voltage-sensing mechanism of BK channels is still under debate. Here, based on gating current measurements, we demonstrate that two arginines in the transmembrane segment S4 (R210 and R213) function as the BK gating charges. Significantly, the energy landscape of the gating particles is electrostatically tuned by a network of salt bridges contained in the voltage sensor domain (VSD). Molecular dynamics simulations and proton transport experiments in the hyperpolarization-activated R210H mutant suggest that the electric field drops off within a narrow septum whose boundaries are defined by the gating charges. Unlike Kv channels, the charge movement in BK appears to be limited to a small displacement of the guanidinium moieties of R210 and R213, without significant movement of the S4.",

keywords = "allosterism, BK channels, potassium channels, voltage sensitivity",

author = "Willy Carrasquel-Ursulaez and Ignacio Segura and Ignacio D{\'i}az-Franulic and Felipe Echeverr{\'i}a and Yenisleidy Lorenzo-Ceballos and Nicol{\'a}s Espinoza and Maximiliano Rojas and Garate, {Jose Antonio} and Eduardo Perozo and Osvaldo Alvarez and Gonzalez-Nilo, {Fernando D.} and Ram{\'o}n Latorre",

note = "Publisher Copyright: Copyright {\textcopyright} 2022 the Author(s). Published by PNAS.",

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Carrasquel-Ursulaez, W, Segura, I, Díaz-Franulic, I, Echeverría, F, Lorenzo-Ceballos, Y, Espinoza, N, Rojas, M, Garate, JA, Perozo, E, Alvarez, O, Gonzalez-Nilo, FD & Latorre, R 2022, 'Mechanism of voltage sensing in Ca²⁺- and voltage-activated K⁺ (BK) channels', Proceedings of the National Academy of Sciences of the United States of America, vol. 119, no. 25, e2204620119. https://doi.org/10.1073/pnas.2204620119

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T1 - Mechanism of voltage sensing in Ca2+- and voltage-activated K+ (BK) channels

AU - Carrasquel-Ursulaez, Willy

AU - Segura, Ignacio

AU - Díaz-Franulic, Ignacio

AU - Echeverría, Felipe

AU - Lorenzo-Ceballos, Yenisleidy

AU - Espinoza, Nicolás

AU - Rojas, Maximiliano

AU - Garate, Jose Antonio

AU - Perozo, Eduardo

AU - Alvarez, Osvaldo

AU - Gonzalez-Nilo, Fernando D.

AU - Latorre, Ramón

PY - 2022/6/21

Y1 - 2022/6/21

N2 - In neurosecretion, allosteric communication between voltage sensors and Ca2+ binding in BK channels is crucially involved in damping excitatory stimuli. Nevertheless, the voltage-sensing mechanism of BK channels is still under debate. Here, based on gating current measurements, we demonstrate that two arginines in the transmembrane segment S4 (R210 and R213) function as the BK gating charges. Significantly, the energy landscape of the gating particles is electrostatically tuned by a network of salt bridges contained in the voltage sensor domain (VSD). Molecular dynamics simulations and proton transport experiments in the hyperpolarization-activated R210H mutant suggest that the electric field drops off within a narrow septum whose boundaries are defined by the gating charges. Unlike Kv channels, the charge movement in BK appears to be limited to a small displacement of the guanidinium moieties of R210 and R213, without significant movement of the S4.

AB - In neurosecretion, allosteric communication between voltage sensors and Ca2+ binding in BK channels is crucially involved in damping excitatory stimuli. Nevertheless, the voltage-sensing mechanism of BK channels is still under debate. Here, based on gating current measurements, we demonstrate that two arginines in the transmembrane segment S4 (R210 and R213) function as the BK gating charges. Significantly, the energy landscape of the gating particles is electrostatically tuned by a network of salt bridges contained in the voltage sensor domain (VSD). Molecular dynamics simulations and proton transport experiments in the hyperpolarization-activated R210H mutant suggest that the electric field drops off within a narrow septum whose boundaries are defined by the gating charges. Unlike Kv channels, the charge movement in BK appears to be limited to a small displacement of the guanidinium moieties of R210 and R213, without significant movement of the S4.

KW - allosterism

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