Pore dimensions and the role of occupancy in unitary conductance of Shaker K channels

Vista sencilla de ítem
dc.contributor.authorDíaz-Franulic, I.
dc.contributor.authorSepúlveda, R.V.
dc.contributor.authorNavarro-Quezada, N.
dc.contributor.authorGonzález-Nilo, F.
dc.contributor.authorNaranjo, D.
dc.date.accessioned2017-08-17T15:44:57Z
dc.date.available2017-08-17T15:44:57Z
dc.date.issued2015-08
dc.descriptionIndexación: Web of Science; Scopus.es_CL
dc.description.abstractK channels mediate the selective passage of K+ across the plasma membrane by means of intimate interactions with ions at the pore selectivity filter located near the external face. Despite high conservation of the selectivity filter, the K+ transport properties of different K channels vary widely, with the unitary conductance spanning a range of over two orders of magnitude. Mutation of Pro475, a residue located at the cytoplasmic entrance of the pore of the small-intermediate conductance K channel Shaker (Pro475Asp (P475D) or Pro475Gln (P475Q)), increases Shaker's reported. 20-pS conductance by approximately six-and approximately threefold, respectively, without any detectable effect on its selectivity. These findings suggest that the structural determinants underlying the diversity of K channel conductance are distinct from the selectivity filter, making P475D and P475Q excellent probes to identify key determinants of the K channel unitary conductance. By measuring diffusion-limited unitary outward currents after unilateral addition of 2 M sucrose to the internal solution to increase its viscosity, we estimated a pore internal radius of capture of 0.82 for all the three Shaker variants (wild type, P475D, and P475Q). This estimate is consistent with the internal entrance of the Kv1.2/2.1 structure if the effective radius of hydrated K+ is set to 4 A. Unilateral exposure to sucrose allowed us to estimate the internal and external access resistances together with that of the inner pore. We determined that Shaker resistance resides mainly in the inner cavity, whereas only similar to 8% resides in the selectivity filter. To reduce the inner resistance, we introduced additional aspartate residues into the internal vestibule to favor ion occupancy. No aspartate addition raised the maximum unitary conductance, measured at saturating [K+], beyond that of P475D, suggesting an similar to 200-pS conductance ceiling for Shaker. This value is approximately one third of the maximum conductance of the large conductance K (BK) channel (the K channel of highest conductance), reducing the energy gap between their K+ transport rates to similar to 1 kT. Thus, although Shaker's pore sustains ion translocation as the BK channel's does, higher energetic costs of ion stabilization or higher friction with the ion's rigid hydration cage in its narrower aqueous cavity may entail higher resistance.es_CL
dc.description.urihttp://jgp.rupress.org/content/146/2/133
dc.identifier.citationJournal of General Physiology Volume 146, Issue 2, 2015es_CL
dc.identifier.issn0022-1295
dc.identifier.otherDOI: 10.1085/jgp.201411353
dc.identifier.urihttp://repositorio.unab.cl/xmlui/handle/ria/3961
dc.language.isoenes_CL
dc.publisherROCKEFELLER UNIV PRESSes_CL
dc.subjectMolecular-Dynamicses_CL
dc.subjectPotassium Channelses_CL
dc.subjectBK Channelses_CL
dc.subjectSkeletal-Musclees_CL
dc.subjectPermeation Pathwayes_CL
dc.subjectIon Conductiones_CL
dc.subjectSelectivityes_CL
dc.subjectMembranees_CL
dc.subjectSimulationses_CL
dc.subjectActivationes_CL
dc.titlePore dimensions and the role of occupancy in unitary conductance of Shaker K channelses_CL
dc.typeArtículoes_CL
Archivos
Bloque original
Mostrando 1 - 1 de 1
Miniatura
Nombre:
Diaz-Franulic_Pore_dimensions_and_the_role.pdf
Tamaño:
1.88 MB
Formato:
Adobe Portable Document Format
Descripción:
TEXTO COMPLETO INGLES
Descargar
Bloque de licencias
Mostrando 1 - 1 de 1
No hay miniatura disponible
Nombre:
license.txt
Tamaño:
1.71 KB
Formato:
Item-specific license agreed upon to submission
Descripción:
Descargar
Colecciones
Fac.CV - Artículos de Revista