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Published June 15, 2022 | Version v1
Journal article Open

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

Creators

  • 1. Universidad de Valparaíso
  • 2. Universidad Mayor
  • 3. Universidad Andrés Bello
  • 4. University of Chicago

Description

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.

Data availability

All study data are included in the article and/or SI Appendix.

Files

carrasquel-ursulaez-et-al-2022-mechanism-of-voltage-sensing-in-ca2-and-voltage-activated-k-(bk)-channels.pdf

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Additional details

Identifiers

DOI
10.1073/pnas.2204620119
Other
oai:uchicago.tind.io:10417

Funding

Fondo Nacional de Desarrollo Científico y Tecnológico
1190203
Fondo Nacional de Desarrollo Científico y Tecnológico
1170733
Fondo Nacional de Desarrollo Científico y Tecnológico
1221260
Fondo Nacional de Desarrollo Científico y Tecnológico
Postdoctorado
Fondo Nacional de Desarrollo Científico y Tecnológico
PAI7719087
US Army Research Office
W911NF-17-2-0081
US Air Force
FA9550-16-1-0384
National Institutes of Health
GM030376
Iniciativa Científica Milenio-Agencia Nacional de Investigación y Desarrollo
P09-022-F
Iniciativa Científica Milenio-Agencia Nacional de Investigación y Desarrollo
NCN2021
Financiamiento Basal para Centros Científicos y Tecnológicos de Excelencia de ANID
FB210008

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Biochemistry and Molecular Biology
Center(s) or Institute(s)
Grossman Center for Quantitative Biology and Human Behavior