Arachidonic acid effect on the allosteric gating mechanism of BK (Slo1) channels associated with the β1 subunit

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• dc.contributor.author Martín, Pedro
• dc.contributor.author Moncada, Melisa
• dc.contributor.author Castillo, Karen
• dc.contributor.author Orsi, Federico
• dc.contributor.author Ducca, Gerónimo
• dc.contributor.author Fernández-Fernández, José Manuel, 1967-
• dc.contributor.author González, Carlos
• dc.contributor.author Milesi, Verónica
• dc.date.accessioned 2022-02-01T07:32:48Z
• dc.date.issued 2021
• dc.description.abstract Arachidonic acid (AA) is a fatty acid involved in the modulation of several ion channels. Previously, we reported that AA activates the high conductance Ca2+- and voltage-dependent K+ channel (BK) in vascular smooth muscle depending on the expression of the auxiliary β1 subunit. Here, using the patch-clamp technique on BK channel co-expressed with β1 subunit in a heterologous cell expression system, we analyzed whether AA modifies the three functional modules involved in the channel gating: the voltage sensor domain (VSD), the pore domain (PD), and the intracellular calcium sensor domain (CSD). We present evidence that AA activates BK channel in a direct way, inducing VSD stabilization on its active configuration observed as a significant left shift in the Q-V curve obtained from gating currents recordings. Moreover, AA facilitates the channel opening transitions when VSD are at rest, and the CSD are unoccupied. Furthermore, the activation was independent of the intracellular Ca2+ concentration and reduced when the BK channel was co-expressed with the Y74A mutant of the β1 subunit. These results allow us to present new insigths in the mechanism by which AA modulates BK channels co-expressed with its auxiliary β1 subunit.
• dc.description.sponsorship This work was partly supported by UNLP 11X/690 (V.M) and ANPCyT PICT 2014-0603 (P.M.), 2018-2435 (P.M.), Argentina; FONDECYT no. 1180999 (K.C.) and 1180464 (CG) and, the Spanish Ministry of Science and Innovation, the State Research Agency (AEI, Agencia Estatal de Investigación), and FEDER Funds (Fondo Europeo de Desarrollo Regional) (Grants RTI2018-094809-B-I00 to J.M.F-F., and CEX2018-000792-M through the “María de Maeztu” Programme for Units of Excellence in R&D to “Departament de Ciències Experimentals i de la Salut”. Martín P and Milesi V are members of the Carrera del Investigador, CONICET. Moncada M is member of the Carrera del Personal de Apoyo a la Investigación y Desarrollo, CONICET. The Centro Interdisciplinario de Neurociencia de Valparaíso (CINV) is a Millennium Institute supported by the Millennium Scientific Initiative of the Ministerio de Economía, Fomento y Turismo, ICM-MINECOM P09-022-F.
• dc.format.mimetype application/pdf
• dc.identifier.citation Martín P, Moncada M, Castillo K, Orsi F, Ducca G, Fernández-Fernández JM, González C, Milesi V. Arachidonic acid effect on the allosteric gating mechanism of BK (Slo1) channels associated with the β1 subunit. Biochim Biophys Acta Biomembr. 2021;1863(9):183550. DOI: 10.1016/j.bbamem.2021.183550
• dc.identifier.doi http://dx.doi.org/10.1016/j.bbamem.2021.183550
• dc.identifier.issn 0005-2736
• dc.identifier.uri http://hdl.handle.net/10230/52379
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Biochim Biophys Acta Biomembr. 2021;1863(9):183550
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RTI2018-094809-B-I00
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/CEX2018-000792-M
• dc.rights © Elsevier http://dx.doi.org/10.1016/j.bbamem.2021.183550
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.keyword Arachidonic acid
• dc.subject.keyword Big conductance calcium and voltage activated potassium channel
• dc.subject.keyword BK
• dc.subject.keyword Fatty acid
• dc.subject.keyword MaxiK
• dc.subject.keyword Slo1
• dc.subject.keyword Voltage sensor
• dc.subject.keyword β-Auxiliary subunits
• dc.title Arachidonic acid effect on the allosteric gating mechanism of BK (Slo1) channels associated with the β1 subunit
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion