scholarly journals Inositol Trisphosphate Receptor Ca2+ Release Channels

2007 ◽  
Vol 87 (2) ◽  
pp. 593-658 ◽  
Author(s):  
J. Kevin Foskett ◽  
Carl White ◽  
King-Ho Cheung ◽  
Don-On Daniel Mak
Keyword(s):  
Single Channel ◽  
Cell Types ◽  
Inositol Trisphosphate Receptor ◽  
Channel Regulation ◽  
Physiological Processes ◽  
Quantitative Studies ◽  
Numerous Cell ◽  
Trisphosphate Receptor ◽  
Channel Properties ◽  
Structural Aspects

The inositol 1,4,5-trisphosphate (InsP3) receptors (InsP3Rs) are a family of Ca2+ release channels localized predominately in the endoplasmic reticulum of all cell types. They function to release Ca2+ into the cytoplasm in response to InsP3 produced by diverse stimuli, generating complex local and global Ca2+ signals that regulate numerous cell physiological processes ranging from gene transcription to secretion to learning and memory. The InsP3R is a calcium-selective cation channel whose gating is regulated not only by InsP3, but by other ligands as well, in particular cytoplasmic Ca2+. Over the last decade, detailed quantitative studies of InsP3R channel function and its regulation by ligands and interacting proteins have provided new insights into a remarkable richness of channel regulation and of the structural aspects that underlie signal transduction and permeation. Here, we focus on these developments and review and synthesize the literature regarding the structure and single-channel properties of the InsP3R.

scholarly journals Extraocular muscle function is impaired in ryr3−/− mice

2019 ◽  
Vol 151 (7) ◽  
pp. 929-943 ◽  
Author(s):  
Jan Eckhardt ◽  
Christoph Bachmann ◽  
Marijana Sekulic-Jablanovic ◽  
Volker Enzmann ◽  
Ki Ho Park ◽  
...  
Keyword(s):  
Muscle Contraction ◽  
Ryanodine Receptor ◽  
Muscle Function ◽  
Extraocular Muscle ◽  
Calcium Release ◽  
Neuronal Excitability ◽  
Extraocular Muscles ◽  
Inositol Trisphosphate Receptor ◽  
Physiological Processes ◽  
Trisphosphate Receptor

Calcium is an ubiquitous second messenger mediating numerous physiological processes, including muscle contraction and neuronal excitability. Ca2+ is stored in the ER/SR and is released into the cytoplasm via the opening of intracellular inositol trisphosphate receptor and ryanodine receptor calcium channels. Whereas in skeletal muscle, isoform 1 of the RYR is the main channel mediating calcium release from the SR leading to muscle contraction, the function of ubiquitously expressed ryanodine receptor 3 (RYR3) is far from clear; it is not known whether RYR3 plays a role in excitation–contraction coupling. We recently reported that human extraocular muscles express high levels of RYR3, suggesting that such muscles may be useful to study the function of this isoform of the Ca2+ channel. In the present investigation, we characterize the visual function of ryr3−/− mice. We observe that ablation of RYR3 affects both mechanical properties and calcium homeostasis in extraocular muscles. These changes significantly impact vision. Our results reveal for the first time an important role for RYR3 in extraocular muscle function.

Effects of divalent cations on single-channel conduction properties of XenopusIP3 receptor

1998 ◽  
Vol 275 (1) ◽  
pp. C179-C188 ◽  
Author(s):  
Don-On Daniel Mak ◽  
J. Kevin Foskett
Keyword(s):  
Single Channel ◽  
Divalent Cations ◽  
Channel Current ◽  
Current Voltage ◽  
Conduction Pathway ◽  
Wide Range ◽  
Trisphosphate Receptor ◽  
Channel Properties ◽  
Current Blocking ◽  
Conduction Properties

The effects of Mg2+ and Ba2+ on single-channel properties of the inositol 1,4,5-trisphosphate receptor (IP3R) were studied by patch clamp of isolated nuclei from Xenopusoocytes. In 140 mM K+ the IP3R channel kinetics and presence of conductance substates were similar over a range (0–9.5 mM) of free Mg2+. In 0 mM Mg2+ the channel current-voltage ( I-V) relation was linear with conductance of ∼320 pS. Conductance varied slowly and continuously over a wide range (SD ≈ 60 pS) and sometimes fluctuated during single openings. The presence of Mg2+ on either or both sides of the channel reduced the current (blocking constant ∼0.6 mM in symmetrical Mg2+), as well as the range of conductances observed, and made the I-V relation nonlinear (slope conductance ∼120 pS near 0 mV and ∼360 pS at ±70 mV in symmetrical 2.5 mM Mg2+). Ba2+ exhibited similar effects on channel conductance. Mg2+ and Ba2+ permeated the channel with a ratio of permeability of Ba2+ to Mg2+ to K+ of 3.5:2.6:1. These results indicate that divalent cations induce nonlinearity in the I-V relation and reduce current by a mechanism involving permeation block of the IP3R due to strong binding to site(s) in the conduction pathway. Furthermore, stabilization of conductance by divalent cations reveals a novel interaction between the cations and the IP3R.

scholarly journals Statistical analysis of modal gating in ion channels

2014 ◽  
Vol 470 (2166) ◽  
pp. 20140030 ◽  
Author(s):  
Ivo Siekmann ◽  
James Sneyd ◽  
Edmund J. Crampin
Keyword(s):  
Ion Channels ◽  
Single Channel ◽  
Channel Activity ◽  
Experimental Conditions ◽  
Inositol Trisphosphate Receptor ◽  
Statistical Framework ◽  
Modal Gating ◽  
Opening And Closing ◽  
Trisphosphate Receptor ◽  
Different Levels

Ion channels regulate the concentrations of ions within cells. By stochastically opening and closing its pore, they enable or prevent ions from crossing the cell membrane. However, rather than opening with a constant probability, many ion channels switch between several different levels of activity even if the experimental conditions are unchanged. This phenomenon is known as modal gating: instead of directly adapting its activity, the channel seems to mix sojourns in active and inactive modes in order to exhibit intermediate open probabilities. Evidence is accumulating that modal gating rather than modulation of opening and closing at a faster time scale is the primary regulatory mechanism of ion channels. However, currently, no method is available for reliably calculating sojourns in different modes. In order to address this challenge, we develop a statistical framework for segmenting single-channel datasets into segments that are characteristic for particular modes. The algorithm finds the number of mode changes, detects their locations and infers the open probabilities of the modes. We apply our approach to data from the inositol-trisphosphate receptor. Based upon these results, we propose that mode changes originate from alternative conformational states of the channel protein that determine a certain level of channel activity.

Characterization of transepithelial potential oscillations in theDrosophilaMalpighian tubule

2001 ◽  
Vol 204 (17) ◽  
pp. 3075-3084 ◽  
Author(s):  
Edward M. Blumenthal
Keyword(s):  
Calcium Release ◽  
Chloride Concentration ◽  
Malpighian Tubule ◽  
Stellate Cells ◽  
Cell Types ◽  
Chloride Conductance ◽  
Potential Oscillations ◽  
Inositol Trisphosphate Receptor ◽  
Transepithelial Potential ◽  
Trisphosphate Receptor

SUMMARYThe Malpighian tubule of Drosophila melanogaster is a useful model system for studying the regulation of epithelial ion transport. In acutely isolated tubules, the transepithelial potential (TEP) undergoes large oscillations in amplitude with a period of approximately 30s. The TEP oscillations are diminished by reductions in the peritubular chloride concentration in a manner consistent with their being caused by fluctuations in chloride conductance. The oscillations are eliminated by pretreating tubules with the calcium chelator BAPTA-AM, although removal of peritubular calcium has no effect, suggesting that the oscillations are a result of either the release of calcium from intracellular stores or the entry of calcium from the tubule lumen. Transcripts encoding two calcium-release channels, the ryanodine receptor and the inositol trisphosphate receptor, are detectable in the tubule by reverse transcription–polymerase chain reaction. To identify the cell type responsible for the oscillations, tubules were treated with diuretic hormones known to alter calcium levels in each of the two cell types. Leucokinin-IV, which increases calcium levels in the stellate cells, suppressed the oscillations, whereas cardioacceleratory peptide 2b (CAP2b), which increases calcium levels in the principal cells, had no effect. These data are consistent with a model in which rhythmic changes in transepithelial chloride conductance, regulated by intracellular calcium levels in the stellate cells, cause the TEP oscillations.

scholarly journals Etiology of the membrane potential of rat white fat adipocytes

2014 ◽  
Vol 307 (2) ◽  
pp. E161-E175 ◽  
Author(s):  
Donna C. Bentley ◽  
Pawitra Pulbutr ◽  
Sue Chan ◽  
Paul A. Smith
Keyword(s):  
Membrane Potential ◽  
Single Channel ◽  
Reversal Potential ◽  
Anion Channel ◽  
Equilibrium Potential ◽  
Physiological Processes ◽  
Cation Permeability ◽  
Intracellular Ca ◽  
White Fat ◽  
Channel Properties

The plasma membrane potential ( Vm) is key to many physiological processes; however, its ionic etiology in white fat adipocytes is poorly characterized. To address this question, we employed the perforated patch current clamp and cell-attached patch clamp methods in isolated primary white fat adipocytes and their cellular model 3T3-L1. The resting Vm of primary and 3T3-L1 adipocytes were −32.1 ± 1.2 mV ( n = 95) and −28.8 ± 1.2 mV ( n = 87), respectively. Vm was independent of cell size and fat content. Elevation of extracellular K+ to 50 mM by equimolar substitution of bath Na+ did not affect Vm, whereas substitution of bath Na+ with the membrane-impermeant cation N-methyl-d-glucamine+-hyperpolarized Vm by 16 mV, data indicative of a nonselective cation permeability. Substitution of 133 mM extracellular Cl− with gluconate-depolarized Vm by 25 mV, whereas Cl− substitution with I− caused a −9 mV hyperpolarization. Isoprenaline (10 μM), but not insulin (100 nM), significantly depolarized Vm. Single-channel ion activity was voltage independent; currents were indicative for Cl− with an inward slope conductance of 16 ± 1.3 pS ( n = 11) and a reversal potential close to the Cl− equilibrium potential, −29 ± 1.6 mV. Although the reduction of extracellular Cl− elevated the intracellular Ca2+ of adipocytes, this was not as large as that produced by elevation of extracellular K+. In conclusion, the Vm of white fat adipocytes is well described by the Goldman-Hodgkin-Katz equation with a predominant permeability to Cl−, where its biophysical and single-channel properties suggest a volume-sensitive anion channel identity. Consequently, changes in serum Cl− homeostasis or the adipocyte's permeability to this anion via drugs will affect its Vm, intracellular Ca2+, and ultimately its function and its role in metabolic control.

scholarly journals A Kinetic Model of the Inositol Trisphosphate Receptor Based on Single-Channel Data

2009 ◽  
Vol 96 (10) ◽  
pp. 4053-4062 ◽  
Author(s):  
Elan Gin ◽  
Martin Falcke ◽  
Larry E. Wagner ◽  
David I. Yule ◽  
James Sneyd
Keyword(s):  
Kinetic Model ◽  
Single Channel ◽  
Inositol Trisphosphate ◽  
Inositol Trisphosphate Receptor ◽  
Trisphosphate Receptor

scholarly journals ER-luminal [Ca2+] regulation of InsP3 receptor gating mediated by an ER-luminal peripheral Ca2+-binding protein

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Horia Vais ◽  
Min Wang ◽  
Karthik Mallilankaraman ◽  
Riley Payne ◽  
Chris McKennan ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Binding Protein ◽  
Annexin A1 ◽  
Channel Activity ◽  
Physiological Processes ◽  
Inositol 1,4,5 Trisphosphate ◽  
Numerous Cell ◽  
Trisphosphate Receptor ◽  
Global And Local ◽  
Luminal Region

Modulating cytoplasmic Ca2+ concentration ([Ca2+]i) by endoplasmic reticulum (ER)-localized inositol 1,4,5-trisphosphate receptor (InsP3R) Ca2+-release channels is a universal signaling pathway that regulates numerous cell-physiological processes. Whereas much is known regarding regulation of InsP3R activity by cytoplasmic ligands and processes, its regulation by ER-luminal Ca2+ concentration ([Ca2+]ER) is poorly understood and controversial. We discovered that the InsP3R is regulated by a peripheral membrane-associated ER-luminal protein that strongly inhibits the channel in the presence of high, physiological [Ca2+]ER. The widely-expressed Ca2+-binding protein annexin A1 (ANXA1) is present in the nuclear envelope lumen and, through interaction with a luminal region of the channel, can modify high-[Ca2+]ER inhibition of InsP3R activity. Genetic knockdown of ANXA1 expression enhanced global and local elementary InsP3-mediated Ca2+ signaling events. Thus, [Ca2+]ER is a major regulator of InsP3R channel activity and InsP3R-mediated [Ca2+]i signaling in cells by controlling an interaction of the channel with a peripheral membrane-associated Ca2+-binding protein, likely ANXA1.

scholarly journals Isoform diversity of the inositol trisphosphate receptor in cell types of mouse origin

1997 ◽  
Vol 322 (2) ◽  
pp. 575-583 ◽  
Author(s):  
Humbert De SMEDT ◽  
Ludwig MISSIAEN ◽  
Jan B. PARYS ◽  
Robert H. HENNING ◽  
Ilse SIENAERT ◽  
...  
Keyword(s):  
Cultured Cells ◽  
Cell Types ◽  
Immunoblot Analysis ◽  
Mouse Cell ◽  
Rt Pcr ◽  
Inositol Trisphosphate Receptor ◽  
Isoform Diversity ◽  
Mouse Cells ◽  
Polymerase Chain ◽  
Trisphosphate Receptor

Previous reports suggested the expression of four or five different Ins(1,4,5)P3 receptor [Ins(1,4,5)P3R] isoforms in mouse cells [Ross, Danoff, Schell, Snyder and Ullrich (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 4265–4269; De Smedt, Missiaen, Parys, Bootman, Mertens, Van Den Bosch and Casteels (1994) J. Biol. Chem. 269, 21691–21698]. To explore this diversity further, we have isolated and sequenced partial clones of two Ins(1,4,5)P3R mRNAs from the mouse embryonic C3H10T½ cell line. These clones showed between 94.2 and 94.9% sequence identity with the corresponding rat Ins(1,4,5)P3R-II and Ins(1,4,5)P3R-III isoforms. Based on these newly obtained sequences we have determined the relative expression of the different Ins(1,4,5)P3R mRNAs in cultured cells and in animal tissues of mouse origin by a ratio reverse transcriptase polymerase chain reaction (RT-PCR). Ins(1,4,5)P3R-I was very prominent in brain and cerebellum and Ins(1,4,5)P3R-II in epithelia such as kidney as well as in both cardiac and skeletal muscle. Ins(1,4,5)P3R-III was highly expressed in all cultured cell types and in tissues with high cell turnover, e.g. testis. The prominent expression of Ins(1,4,5)P3R-I and Ins(1,4,5)P3R-III in A7r5 and C3H10T½ cells respectively was confirmed by immunoblot analysis and was compatible with a lower threshold for Ins(1,4,5)P3-induced Ca2+ release in the former cell type. Screening of a large number of mouse cell lines and tissues revealed the presence of Ins(1,4,5)P3R-I as well as of the Ins(1,4,5)P3R-II and Ins(1,4,5)P3R-III isoforms which were identified in the present study, but in contrast with previous reports there was no evidence for more isoform diversity.

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