The voltage sensor is responsible for ~pH dependence in Hv 1 channels

dc.contributor.authorCarmona, Emerson M.
dc.contributor.authorFernandez, Miguel
dc.contributor.authorAlvear-Arias, Juan J.
dc.contributor.authorNeely, Alan
dc.contributor.authorLarsson, H. Peter
dc.contributor.authorAlvarez, Osvaldo
dc.contributor.authorGarate, Jose Antonio
dc.contributor.authorLatorre, Ramon
dc.contributor.authorGonzalez, Carlos
dc.date.accessioned2022-11-30T02:46:14Z
dc.date.available2022-11-30T02:46:14Z
dc.date.issued2021
dc.description.abstractThe dissipation of acute acid loads by the voltage-gated proton channel (Hv1) relies on regulating the channel’s open probability by the voltage and the ΔpH across the membrane (ΔpH = pHex − pHin). Using monomeric Ciona-Hv1, we asked whether ΔpH-dependent gating is produced during the voltage sensor activation or permeation pathway opening. A leftward shift of the conductance-voltage (G-V) curve was produced at higher ΔpH values in the monomeric channel. Next, we measured the voltage sensor pH dependence in the absence of a functional permeation pathway by recording gating currents in the monomeric nonconducting D160N mutant. Increasing the ΔpH leftward shifted the gating charge-voltage (Q-V) curve, demonstrating that the ΔpH-dependent gating in Hv1 arises by modulating its voltage sensor. We fitted our data to a model that explicitly supposes the Hv1 voltage sensor free energy is a function of both the proton chemical and the electrical potential. The parameters obtained showed that around 60% of the free energy stored in the ΔpH is coupled to the Hv1 voltage sensor activation. Our results suggest that the molecular mechanism underlying the Hv1 ΔpH dependence is produced by protons, which alter the free-energy landscape around the voltage sensor domain. We propose that this alteration is produced by accessibility changes of the protons in the Hv1 voltage sensor during activation.en_ES
dc.facultadFacultad de Cienciasen_ES
dc.file.nameCarmona_Vol2021.pdf
dc.identifier.doihttps://doi.org/10.1073/pnas.2025556118
dc.identifier.urihttp://repositoriobibliotecas.uv.cl/handle/uvscl/7269
dc.languageen
dc.publisherNational Academy Of Science
dc.sourceProceedings of the National Academy of Sciences (PNAS)
dc.subjectPH DEPENDENCEen_ES
dc.subjectVOLTAGE SENSORen_ES
dc.subjectGATING CURRENTSen_ES
dc.subjectHV1en_ES
dc.subjectCOUPLINGen_ES
dc.titleThe voltage sensor is responsible for ~pH dependence in Hv 1 channels
dc.typeArticulo
uv.departamentoCentro Interdisciplinario de Neurociencia de Valparaiso

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