| dc.creator | Foskett,J. Kevin | |
| dc.creator | Mak,D.-O. Daniel | |
| dc.date | 2004-01-01 | |
| dc.date.accessioned | 2020-02-17T15:35:42Z | |
| dc.date.available | 2020-02-17T15:35:42Z | |
| dc.identifier | https://scielo.conicyt.cl/scielo.php?script=sci_arttext&pid=S0716-97602004000400004 | |
| dc.identifier.uri | https://revistaschilenas.uchile.cl/handle/2250/132035 | |
| dc.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. | |
| dc.format | text/html | |
| dc.language | en | |
| dc.publisher | Sociedad de Biología de Chile | |
| dc.relation | 10.4067/S0716-97602004000400004 | |
| dc.rights | info:eu-repo/semantics/openAccess | |
| dc.source | Biological Research v.37 n.4 2004 | |
| dc.subject | InsP3 receptor | |
| dc.subject | calcium release channel | |
| dc.subject | calcium | |
| dc.subject | ion channel | |
| dc.subject | model | |
| dc.title | Novel model of calcium and inositol 1,4,5-trisphosphate regulation of InsP3 receptor channel gating in native endoplasmic reticulum | |
