Rapid kinetics of myo-inositol trisphosphate binding and dissociation in cerebellar microsomes.

Hannaert-Merah, Zalika; Coquil, Jean-François; Combettes, Laurent; Claret, M; Mauger, Jean‐Pierre; Champeil, Philippe

doi:10.1016/s0021-9258(18)43929-4

Cited by 36 publications

(9 citation statements)

References 47 publications

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“…receptor. This argument is further supported by the results from rapid analyses of 3 H-IP 3 binding to the receptor [24], from which we estimate the half-time for association of 56 M IP 3 (see above) to be less than 400 sec.…”

Section: Delayed Opening Of Ip 3 Receptorssupporting

confidence: 66%

“…As with any receptor-ligand interaction, the rate of association of IP 3 with its receptor is expected to increase with IP 3 concentration [24]. Our observation that a substantial increase in IP 3 concentration failed to reduce the absolute latency before channel opening therefore indicates that the delay is not due to the kinetics of IP 3 binding to its Peak rates of IP 3 -evoked Ca 2+ release occur after substantial delays.…”

Section: Delayed Opening Of Ip 3 Receptorsmentioning

confidence: 71%

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Cooperative activation of IP3 receptors by sequential binding of IP3 and Ca2+ safeguards against spontaneous activity

1997

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We propose that the closed conformation of the IP3 receptor is very stable and therefore minimally susceptible to spontaneous activation; at least three (probably four) IP3 molecules may be required to provide enough binding energy to drive the receptor into a stable open conformation. We suggest that a further defence from noise is provided by an extreme form of coincidence detection. Binding of IP3 to each of its four receptor subunits unmasks a site to which Ca2+ must bind before the channel can open. As IP3 binding may also initiate receptor inactivation, there may be only a narrow temporal window during which each receptor subunit must bind both of its agonists if the channel is to open rather than inactivate.

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Section: Delayed Opening Of Ip 3 Receptorssupporting

confidence: 66%

Section: Delayed Opening Of Ip 3 Receptorsmentioning

confidence: 71%

Cooperative activation of IP3 receptors by sequential binding of IP3 and Ca2+ safeguards against spontaneous activity

1997

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“…The inhibition was initially found to be apparent only, and was associated to the activation of an endogenous phospholipase C that produces competitive IP 3 (49) but this scenario was contradicted by subsequent determinations under different conditions (10). In some studies an effective inhibition resulted exclusively from a Ca 21 -mediated decrease of the apparent affinity of the receptor for IP 3 (10,26,50), whereas Cardy et al (29) found the mechanism to be a reduction in the maximal number of IP 3 binding sites with no change in the affinity for IP 3 or the Hill coefficient.…”

Section: Ip 3 Binding To the Er Membranementioning

confidence: 99%

Gating Mechanisms of the Type-1 Inositol Trisphosphate Receptor

Băran

2005

Biophysical Journal

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A large amount of data and observations on inositol 1,4,5-trisphosphate (IP(3)) binding to the IP(3) receptor/Ca(2+) channel, the steady-state activity of the channel, and its inactivation by IP(3) can be explained by assuming one activation and one inhibition module, both allosterically operated by Ca(2+), IP(3), and ATP, and one adaptation element, driven by IP(3), Ca(2+), and the interconversion between two possible conformations of the receptor. The adaptation module becomes completely insensitive to a second IP(3) pulse within 80 s. Observed kinetic responses are well reproduced if, in addition, two module open states are rendered inactive by the current charge carrier Mn(2+). The inactivation time constants are 59 s in the activation, and 0.75 s in the adaptation module. The in vivo open probability of the channel is predicted to be almost in coincidence with the behavior in lipid bilayers for IP(3) levels of 0.2 and 2 microM and one-order-higher at 0.02 microM IP(3), whereas at 180 microM IP(3) the maximal in vivo activity may be 2.5-orders higher than in bilayers and restricted to a narrower Ca(2+) domain (approximately 10 microM-wide versus approximately 100 microM-wide). IP(3) is likely to inhibit channel activity at < or =120 nM Ca(2+) in vivo.

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“…Non-specific binding was determined in the presence of 5 µM InsP $ . After a 5 min incubation period, 0.8 ml of the sample was layered on to a Whatman GF\C glassfibre filter and washed with 1 ml of an ice-cold medium consisting of 250 mM sucrose, 10 mM NaH # PO % and 4 mM EGTA adjusted to pH 8.3, to minimize the dissociation of the ligand-receptor complex [22]. Radioactivity retained on the filters was counted by scintillation spectrometry.…”

Section: Equilibrium [ 3 H]insp 3 -Binding Studies On Membranesmentioning

confidence: 99%

“…In agreement, we observed this effect even when the incubation medium was continuously changed by perfusion. Thus it was at least partly due to direct action of Ca# + on the receptor or on the calmedin and was not secondary to the production of an intermediary metabolite [22]. Subsequently, we investigated the effect of Ca# + on the binding of [$H]InsP $ to cerebellar and cortical membranes.…”

Section: Influence Of the Si Region On The Binding Of Inspmentioning

confidence: 99%

The properties of a subtype of the inositol 1,4,5-trisphosphate receptor resulting from alternative splicing of the mRNA in the ligand-binding domain

Lièvremont

Lancien

Hilly

et al. 1996

Biochemical Journal

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Subtypes of the type-1 inositol 1,4,5-trisphosphate (InsP3) receptor differ at the mRNA level in two small variably spliced segments. One segment (SI) encodes for a sequence within the InsP3-binding domain, thus its presence or absence could affect the functions of the receptor. We have used anti-peptide antibodies to confirm the existence of different subtypes of the InsP3 receptor (InsP3R) protein. The antibody against residues 322-332, within the SI region, recognized a 260 kDa polypeptide in membranes prepared from rat cerebellum or cerebral cortex. The cerebellum contained a few percent of the InsP3R protein having the SI region, whereas the cerebral cortex contained a high proportion of receptors with the SI region. These two tissues were representative of both isoforms, SI- or SI+, and displayed the same [3H]InsP3-binding characteristics. Thus, the SI region was not involved in the basic properties of the receptor. Deletion of the peptide 316-352 containing the SI segment greatly reduced InsP3 binding [Miyawaki, Furuichi, Ryou, Yoshikawa, Nakagawa, Saitoh and Mikoshiba (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 4911-4915]. The antibodies against the SI region or against residues 337-349 did not modify the binding of [3H]InsP3 in the cortical membranes rich in the SI+ isoform or in cerebellar membranes. These results suggested that the SI region was not part of the binding site. The subcellular distribution of these two isoforms was then investigated in rat liver. The two isoforms were identified in different membrane fractions and they followed the same subcellular distribution. We suggest that the domain with the SI region may be involved in a function other than InsP3-induced Ca2+ release.

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Rapid kinetics of myo-inositol trisphosphate binding and dissociation in cerebellar microsomes.

Cited by 36 publications

References 47 publications

Cooperative activation of IP3 receptors by sequential binding of IP3 and Ca2+ safeguards against spontaneous activity

Cooperative activation of IP3 receptors by sequential binding of IP3 and Ca2+ safeguards against spontaneous activity

Gating Mechanisms of the Type-1 Inositol Trisphosphate Receptor

The properties of a subtype of the inositol 1,4,5-trisphosphate receptor resulting from alternative splicing of the mRNA in the ligand-binding domain

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