scholarly journals Differential Regulation of ER Ca2+ Uptake and Release Rates Accounts for Multiple Modes of Ca2+-induced Ca2+ Release

2002 ◽  
Vol 119 (3) ◽  
pp. 211-233 ◽  
Author(s):  
Meredith A. Albrecht ◽  
Stephen L. Colegrove ◽  
David D. Friel
Keyword(s):  
Plasma Membrane ◽  
Sympathetic Neurons ◽  
Surface Membrane ◽  
Central Element ◽  
Differential Regulation ◽  
Transport Systems ◽  
Excitable Cells ◽  
Release Rates ◽  
Multiple Modes ◽  
Uptake And Release

The ER is a central element in Ca2+ signaling, both as a modulator of cytoplasmic Ca2+ concentration ([Ca2+]i) and as a locus of Ca2+-regulated events. During surface membrane depolarization in excitable cells, the ER may either accumulate or release net Ca2+, but the conditions of stimulation that determine which form of net Ca2+ transport occurs are not well understood. The direction of net ER Ca2+ transport depends on the relative rates of Ca2+ uptake and release via distinct pathways that are differentially regulated by Ca2+, so we investigated these rates and their sensitivity to Ca2+ using sympathetic neurons as model cells. The rate of Ca2+ uptake by SERCAs (JSERCA), measured as the t-BuBHQ-sensitive component of the total cytoplasmic Ca2+ flux, increased monotonically with [Ca2+]i. Measurement of the rate of Ca2+ release (JRelease) during t-BuBHQ-induced [Ca2+]i transients made it possible to characterize the Ca2+ permeability of the ER (\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\overline{\mathrm{P}}_{\mathrm{ER}}\) \end{document}), describing the activity of all Ca2+-permeable channels that contribute to passive ER Ca2+ release, including ryanodine-sensitive Ca2+ release channels (RyRs) that are responsible for CICR. Simulations based on experimentally determined descriptions of JSERCA, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\overline{\mathrm{P}}_{\mathrm{ER}}\) \end{document}, and of Ca2+ extrusion across the plasma membrane (Jpm) accounted for our previous finding that during weak depolarization, the ER accumulates Ca2+, but at a rate that is attenuated by activation of a CICR pathway operating in parallel with SERCAs to regulate net ER Ca2+ transport. Caffeine greatly increased the [Ca2+] sensitivity of \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\overline{\mathrm{P}}_{\mathrm{ER}}\) \end{document}, accounting for the effects of caffeine on depolarization-evoked [Ca2+]i elevations and caffeine-induced [Ca2+]i oscillations. Extending the rate descriptions of JSERCA, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\overline{\mathrm{P}}_{\mathrm{ER}}\) \end{document}, and Jpm to higher [Ca2+]i levels shows how the interplay between Ca2+ transport systems with different Ca2+ sensitivities accounts for the different modes of CICR over different ranges of [Ca2+]i during stimulation.

scholarly journals Depolarization-induced Calcium Responses in Sympathetic Neurons: Relative Contributions from Ca2+ Entry, Extrusion, ER/Mitochondrial Ca2+ Uptake and Release, and Ca2+ Buffering

2006 ◽  
Vol 129 (1) ◽  
pp. 29-56 ◽  
Author(s):  
Michael Patterson ◽  
James Sneyd ◽  
David D. Friel
Keyword(s):  
Plasma Membrane ◽  
Voltage Clamp ◽  
Diffusion Model ◽  
Time Course ◽  
Sympathetic Neurons ◽  
Cell Types ◽  
Specific Cell ◽  
Modeling Studies ◽  
Uniform Model ◽  
Uptake And Release

Many models have been developed to account for stimulus-evoked [Ca2+] responses, but few address how responses elicited in specific cell types are defined by the Ca2+ transport and buffering systems that operate in the same cells. In this study, we extend previous modeling studies by linking the time course of stimulus-evoked [Ca2+] responses to the underlying Ca2+ transport and buffering systems. Depolarization-evoked [Ca2+]i responses were studied in sympathetic neurons under voltage clamp, asking how response kinetics are defined by the Ca2+ handling systems expressed in these cells. We investigated five cases of increasing complexity, comparing observed and calculated responses deduced from measured Ca2+ handling properties. In Case 1, [Ca2+]i responses were elicited by small Ca2+ currents while Ca2+ transport by internal stores was inhibited, leaving plasma membrane Ca2+ extrusion intact. In Case 2, responses to the same stimuli were measured while mitochondrial Ca2+ uptake was active. In Case 3, responses were elicited as in Case 2 but with larger Ca2+ currents that produce larger and faster [Ca2+]i elevations. Case 4 included the mitochondrial Na/Ca exchanger. Finally, Case 5 included ER Ca2+ uptake and release pathways. We found that [Ca2+]i responses elicited by weak stimuli (Cases 1 and 2) could be quantitatively reconstructed using a spatially uniform model incorporating the measured properties of Ca2+ entry, removal, and buffering. Responses to strong depolarization (Case 3) could not be described by this model, but were consistent with a diffusion model incorporating the same Ca2+ transport and buffering descriptions, as long as endogenous buffers have low mobility, leading to steep radial [Ca2+]i gradients and spatially nonuniform Ca2+ loading by mitochondria. When extended to include mitochondrial Ca2+ release (Case 4) and ER Ca2+ transport (Case 5), the diffusion model could also account for previous measurements of stimulus-evoked changes in total mitochondrial and ER Ca concentration.

scholarly journals Quantitative Analysis of Mitochondrial Ca2+ Uptake and Release Pathways in Sympathetic Neurons

2000 ◽  
Vol 115 (3) ◽  
pp. 371-388 ◽  
Author(s):  
Stephen L. Colegrove ◽  
Meredith A. Albrecht ◽  
David D. Friel
Keyword(s):  
Plasma Membrane ◽  
Time Course ◽  
Sympathetic Neurons ◽  
Differential Sensitivity ◽  
Rate Equations ◽  
Intact Cells ◽  
Isolated Mitochondria ◽  
Cellular Context ◽  
The Impact ◽  
Uptake And Release

Rate equations for mitochondrial Ca2+ uptake and release and plasma membrane Ca2+ transport were determined from the measured fluxes in the preceding study and incorporated into a model of Ca2+ dynamics. It was asked if the measured fluxes are sufficient to account for the [Ca2+]i recovery kinetics after depolarization-evoked [Ca2+]i elevations. Ca2+ transport across the plasma membrane was described by a parallel extrusion/leak system, while the rates of mitochondrial Ca2+ uptake and release were represented using equations like those describing Ca2+ transport by isolated mitochondria. Taken together, these rate descriptions account very well for the time course of recovery after [Ca2+]i elevations evoked by weak and strong depolarization and their differential sensitivity to FCCP, CGP 37157, and [Na+]i. The model also leads to three general conclusions about mitochondrial Ca2+ transport in intact cells: (1) mitochondria are expected to accumulate Ca2+ even in response to stimuli that raise [Ca2+]i only slightly above resting levels; (2) there are two qualitatively different stimulus regimes that parallel the buffering and non-buffering modes of Ca2+ transport by isolated mitochondria that have been described previously; (3) the impact of mitochondrial Ca2+ transport on intracellular calcium dynamics is strongly influenced by nonmitochondrial Ca2+ transport; in particular, the magnitude of the prolonged [Ca2+]i elevation that occurs during the plateau phase of recovery is related to the Ca2+ set-point described in studies of isolated mitochondria, but is a property of mitochondrial Ca2+ transport in a cellular context. Finally, the model resolves the paradoxical finding that stimulus-induced [Ca2+]i elevations as small as ∼300 nM increase intramitochondrial total Ca2+ concentration, but the steady [Ca2+]i elevations evoked by such stimuli are not influenced by FCCP.

scholarly journals Dissection of Mitochondrial Ca2+ Uptake and Release Fluxes in Situ after Depolarization-Evoked [Ca2+]i Elevations in Sympathetic Neurons

2000 ◽  
Vol 115 (3) ◽  
pp. 351-370 ◽  
Author(s):  
Stephen L. Colegrove ◽  
Meredith A. Albrecht ◽  
David D. Friel
Keyword(s):  
Plasma Membrane ◽  
Initial Phase ◽  
Sympathetic Neurons ◽  
Low Frequency ◽  
Selective Inhibitor ◽  
Atp Production ◽  
Exchange Inhibitor ◽  
Simple Dependence ◽  
Uptake And Release

We studied how mitochondrial Ca2+ transport influences [Ca2+]i dynamics in sympathetic neurons. Cells were treated with thapsigargin to inhibit Ca2+ accumulation by SERCA pumps and depolarized to elevate [Ca2+]i; the recovery that followed repolarization was then examined. The total Ca2+ flux responsible for the [Ca2+]i recovery was separated into mitochondrial and nonmitochondrial components based on sensitivity to the proton ionophore FCCP, a selective inhibitor of mitochondrial Ca2+ transport in these cells. The nonmitochondrial flux, representing net Ca2+ extrusion across the plasma membrane, has a simple dependence on [Ca2+]i, while the net mitochondrial flux (Jmito) is biphasic, indicative of Ca2+ accumulation during the initial phase of recovery when [Ca2+]i is high, and net Ca2+ release during later phases of recovery. During each phase, mitochondrial Ca2+ transport has distinct effects on recovery kinetics. Jmito was separated into components representing mitochondrial Ca2+ uptake and release based on sensitivity to the specific mitochondrial Na+/Ca2+ exchange inhibitor, CGP 37157 (CGP). The CGP-resistant (uptake) component of Jmito increases steeply with [Ca2+]i, as expected for transport by the mitochondrial uniporter. The CGP-sensitive (release) component is inhibited by lowering the intracellular Na+ concentration and depends on both intra- and extramitochondrial Ca2+ concentration, as expected for the Na+/Ca2+ exchanger. Above ∼400 nM [Ca2+]i, net mitochondrial Ca2+ transport is dominated by uptake and is largely insensitive to CGP. When [Ca2+]i is ∼200–300 nM, the net mitochondrial flux is small but represents the sum of much larger uptake and release fluxes that largely cancel. Thus, mitochondrial Ca2+ transport occurs in situ at much lower concentrations than previously thought, and may provide a mechanism for quantitative control of ATP production after brief or low frequency stimuli that raise [Ca2+]i to levels below ∼500 nM.

scholarly journals Differential regulation of the GLUT-1 and GLUT-4 glucose transport systems by glucose and insulin in L6 muscle cells in culture

1991 ◽  
Vol 266 (4) ◽  
pp. 2615-2621 ◽  
Author(s):  
U M Koivisto ◽  
H Martinez-Valdez ◽  
P J Bilan ◽  
E Burdett ◽  
T Ramlal ◽  
...  
Keyword(s):  
Glucose Transport ◽  
Muscle Cells ◽  
Differential Regulation ◽  
Transport Systems ◽  
Glut 1 ◽  
Glut 4 ◽  
Cells In Culture ◽  
L6 Muscle Cells

Vehicular Edge Computing: Architecture, Resource Management, Security, and Challenges

2023 ◽  
Vol 55 (1) ◽  
pp. 1-46
Author(s):  
Rodolfo Meneguette ◽  
Robson De Grande ◽  
Jo Ueyama ◽  
Geraldo P. Rocha Filho ◽  
Edmundo Madeira
Keyword(s):  
Smart City ◽  
Central Element ◽  
Edge Computing ◽  
Transport Systems ◽  
Vehicular Communication ◽  
Intelligent Transport Systems ◽  
Urban Computing ◽  
Intelligent Transport ◽  
Content Caching ◽  
Computational Resources

Vehicular Edge Computing (VEC), based on the Edge Computing motivation and fundamentals, is a promising technology supporting Intelligent Transport Systems services, smart city applications, and urban computing. VEC can provide and manage computational resources closer to vehicles and end-users, providing access to services at lower latency and meeting the minimum execution requirements for each service type. This survey describes VEC’s concepts and technologies; we also present an overview of existing VEC architectures, discussing them and exemplifying them through layered designs. Besides, we describe the underlying vehicular communication in supporting resource allocation mechanisms. With the intent to overview the risks, breaches, and measures in VEC, we review related security approaches and methods. Finally, we conclude this survey work with an overview and study of VEC’s main challenges. Unlike other surveys in which they are focused on content caching and data offloading, this work proposes a taxonomy based on the architectures in which VEC serves as the central element. VEC supports such architectures in capturing and disseminating data and resources to offer services aimed at a smart city through their aggregation and the allocation in a secure manner.

scholarly journals The secretory pathway of bovine platelets

Blood ◽  
1987 ◽  
Vol 69 (3) ◽  
pp. 878-885 ◽  
Author(s):  
JG White
Keyword(s):  
Plasma Membrane ◽  
Secretory Pathway ◽  
Human Platelet ◽  
Surface Membrane ◽  
Surrounding Medium ◽  
Human Platelets ◽  
Resting Cells ◽  
Granule Secretion ◽  
New Perspective ◽  
Platelet Secretion

Abstract Human platelets contain tortuous channels in their cytoplasm, the surface-connected or open canalicular system (OCS), that communicate directly with the surrounding medium through openings on the surface membrane. Some workers have suggested that the OCS serves as the egress route for products secreted during the release reaction. Others have proposed alternate secretory pathways. Since bovine platelets lack the OCS found in human cells, the present study has examined the secretory mechanism of these cells to see whether it can shed light on the mystery of human platelet secretion. Bovine platelet granules, in contrast to human granules, are located more peripherally in resting cells (often in contact with the plasma membrane), most do not move centrally following thrombin stimulation as do human platelet granules, and many fuse directly with the external plasma membrane without any intermediate channel. The lack of peripheral location of human granules, their central rather than peripheral movement during secretion, and the presence of extensive channels are all consistent with the larger importance of the secretory channel to human platelets. Thus, though studies of bovine secretion do show that platelets can secrete their granules by direct fusion of granule and surface membranes, other differences from human platelets emphasize that this pathway, although important to bovine platelet secretion, is less important in human platelets. Studies of bovine platelets also show that the OCS is more dynamic than might have been considered from human studies and can form rapidly in response to stimulation. Such newly formed channels are used as a conduit for secretion of granule contents. The finding emphasizes the importance of channels for granule secretion in platelets generally and puts a new perspective on the ability of these cells to form channels rapidly in response to stimulation.

scholarly journals An ABC transporter Wzm–Wzt catalyzes translocation of lipid-linked galactan across the plasma membrane in mycobacteria

2021 ◽  
Vol 118 (17) ◽  
pp. e2023663118
Author(s):  
Karin Savková ◽  
Stanislav Huszár ◽  
Peter Baráth ◽  
Zuzana Pakanová ◽  
Stanislav Kozmon ◽  
...  
Keyword(s):  
Cell Wall ◽  
Plasma Membrane ◽  
Abc Transporter ◽  
Morphological Changes ◽  
Transport Systems ◽  
Host Immune System ◽  
Mycolic Acids ◽  
Cell Wall Biogenesis ◽  
Covalently Linked ◽  
High Level

Mycobacterium tuberculosis, one of the deadliest pathogens in human history, is distinguished by a unique, multilayered cell wall, which offers the bacterium a high level of protection from the attacks of the host immune system. The primary structure of the cell wall core, composed of covalently linked peptidoglycan, branched heteropolysaccharide arabinogalactan, and mycolic acids, is well known, and numerous enzymes involved in the biosynthesis of its components are characterized. The cell wall biogenesis takes place at both cytoplasmic and periplasmic faces of the plasma membrane, and only recently some of the specific transport systems translocating the metabolic intermediates between these two compartments have been characterized [M. Jackson, C. M. Stevens, L. Zhang, H. I. Zgurskaya, M. Niederweis, Chem. Rev., 10.1021/acs.chemrev.0c00869 (2020)]. In this work, we use CRISPR interference methodology in Mycobacterium smegmatis to functionally characterize an ATP-binding cassette (ABC) transporter involved in the translocation of galactan precursors across the plasma membrane. We show that genetic knockdown of the transmembrane subunit of the transporter results in severe morphological changes and the accumulation of an aberrantly long galactan precursor. Based on similarities with structures and functions of specific O-antigen ABC transporters of gram-negative bacteria [C. Whitfield, D. M. Williams, S. D. Kelly, J. Biol. Chem. 295, 10593-10609 (2020)], we propose a model for coupled synthesis and export of the galactan polymer precursor in mycobacteria.

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