Novel model of calcium and inositol 1,4,5-trisphosphate regulation of InsP3 receptor channel gating in native endoplasmic reticulum
The InsP3R Ca2+-release channel has biphasic dependence on cytoplasmic free Ca2+ concentration ([Ca2+]i). InsP3 activates gating primarily by reducing high [Ca2+]i inhibition. To determine whether relieving Ca2+ inhibition is sufficient for activation, we examined single-channels in low [Ca2+]i in t...
Guardado en:
| Autores principales: | , |
|---|---|
| Lenguaje: | English |
| Publicado: |
Sociedad de Biología de Chile
2004
|
| Materias: | |
| Acceso en línea: | http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602004000400004 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:scielo:S0716-97602004000400004 |
|---|---|
| record_format |
dspace |
| spelling |
oai:scielo:S0716-976020040004000042005-06-02Novel model of calcium and inositol 1,4,5-trisphosphate regulation of InsP3 receptor channel gating in native endoplasmic reticulumFoskett,J. KevinMak,D.-O. Daniel InsP3 receptor calcium release channel calcium ion channel model The InsP3R Ca2+-release channel has biphasic dependence on cytoplasmic free Ca2+ concentration ([Ca2+]i). InsP3 activates gating primarily by reducing high [Ca2+]i inhibition. To determine whether relieving Ca2+ inhibition is sufficient for activation, we examined single-channels in low [Ca2+]i in the absence of InsP3 by patch clamping isolated Xenopus oocyte nuclei. For both endogenous Xenopus type 1 and recombinant rat type 3 InsP3R channels, spontaneous InsP3-independent activities with low open probability Po (~ 0.03) were observed in [Ca2+]i < 5 nM, whereas none were observed in 25 nM Ca2+. These results establish the half-maximal inhibitory [Ca2+]i in the absence of InsP3 and demonstrate that the channel can be active when all of its ligand-binding sites are unoccupied. In the simplest allosteric model that fits all observations in nuclear patch-clamp studies, the tetrameric channel can adopt six conformations, the equilibria among which are controlled by two inhibitory, one activating Ca2+-binding, and one InsP3-binding sites in a manner similar to the Monod-Wyman-Changeux model. InsP3 binding activates gating by affecting the relative affinity for Ca2+ of one of the inhibitory sites in different channel conformations, transforming it into an activating site. Ca2+ inhibition of InsP3-liganded channels is mediated by an InsP3-independent second inhibitory site.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.37 n.4 20042004-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602004000400004en10.4067/S0716-97602004000400004 |
| institution |
Scielo Chile |
| collection |
Scielo Chile |
| language |
English |
| topic |
InsP3 receptor calcium release channel calcium ion channel model |
| spellingShingle |
InsP3 receptor calcium release channel calcium ion channel model Foskett,J. Kevin Mak,D.-O. Daniel Novel model of calcium and inositol 1,4,5-trisphosphate regulation of InsP3 receptor channel gating in native endoplasmic reticulum |
| description |
The InsP3R Ca2+-release channel has biphasic dependence on cytoplasmic free Ca2+ concentration ([Ca2+]i). InsP3 activates gating primarily by reducing high [Ca2+]i inhibition. To determine whether relieving Ca2+ inhibition is sufficient for activation, we examined single-channels in low [Ca2+]i in the absence of InsP3 by patch clamping isolated Xenopus oocyte nuclei. For both endogenous Xenopus type 1 and recombinant rat type 3 InsP3R channels, spontaneous InsP3-independent activities with low open probability Po (~ 0.03) were observed in [Ca2+]i < 5 nM, whereas none were observed in 25 nM Ca2+. These results establish the half-maximal inhibitory [Ca2+]i in the absence of InsP3 and demonstrate that the channel can be active when all of its ligand-binding sites are unoccupied. In the simplest allosteric model that fits all observations in nuclear patch-clamp studies, the tetrameric channel can adopt six conformations, the equilibria among which are controlled by two inhibitory, one activating Ca2+-binding, and one InsP3-binding sites in a manner similar to the Monod-Wyman-Changeux model. InsP3 binding activates gating by affecting the relative affinity for Ca2+ of one of the inhibitory sites in different channel conformations, transforming it into an activating site. Ca2+ inhibition of InsP3-liganded channels is mediated by an InsP3-independent second inhibitory site. |
| author |
Foskett,J. Kevin Mak,D.-O. Daniel |
| author_facet |
Foskett,J. Kevin Mak,D.-O. Daniel |
| author_sort |
Foskett,J. Kevin |
| title |
Novel model of calcium and inositol 1,4,5-trisphosphate regulation of InsP3 receptor channel gating in native endoplasmic reticulum |
| title_short |
Novel model of calcium and inositol 1,4,5-trisphosphate regulation of InsP3 receptor channel gating in native endoplasmic reticulum |
| title_full |
Novel model of calcium and inositol 1,4,5-trisphosphate regulation of InsP3 receptor channel gating in native endoplasmic reticulum |
| title_fullStr |
Novel model of calcium and inositol 1,4,5-trisphosphate regulation of InsP3 receptor channel gating in native endoplasmic reticulum |
| title_full_unstemmed |
Novel model of calcium and inositol 1,4,5-trisphosphate regulation of InsP3 receptor channel gating in native endoplasmic reticulum |
| title_sort |
novel model of calcium and inositol 1,4,5-trisphosphate regulation of insp3 receptor channel gating in native endoplasmic reticulum |
| publisher |
Sociedad de Biología de Chile |
| publishDate |
2004 |
| url |
http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602004000400004 |
| work_keys_str_mv |
AT foskettjkevin novelmodelofcalciumandinositol145trisphosphateregulationofinsp3receptorchannelgatinginnativeendoplasmicreticulum AT makdodaniel novelmodelofcalciumandinositol145trisphosphateregulationofinsp3receptorchannelgatinginnativeendoplasmicreticulum |
| _version_ |
1718441373420486656 |