Mitochondrial Channels: Ion Fluxes and More

2014 ◽  
Vol 94 (2) ◽  
pp. 519-608 ◽  
Author(s):  
Ildiko Szabo ◽  
Mario Zoratti
Keyword(s):  
Ion Channels ◽  
Molecular Identification ◽  
Cell Biology ◽  
Energy Supply ◽  
Integrative Approach ◽  
Mitochondrial Channels ◽  
Electrophysiological Properties ◽  
Molecular Identity ◽  
Substantial Progress ◽  
Entire Cell

The field of mitochondrial ion channels has recently seen substantial progress, including the molecular identification of some of the channels. An integrative approach using genetics, electrophysiology, pharmacology, and cell biology to clarify the roles of these channels has thus become possible. It is by now clear that many of these channels are important for energy supply by the mitochondria and have a major impact on the fate of the entire cell as well. The purpose of this review is to provide an up-to-date overview of the electrophysiological properties, molecular identity, and pathophysiological functions of the mitochondrial ion channels studied so far and to highlight possible therapeutic perspectives based on current information.

scholarly journals A microscopic view of the cell

2016 ◽  
Vol 27 (21) ◽  
pp. 3183-3184
Author(s):  
Bo Huang
Keyword(s):  
Quantitative Analysis ◽  
Light Microscopy ◽  
Cell Biology ◽  
Integrative Approach ◽  
Biological Knowledge ◽  
Critical Links ◽  
Indispensable Tool ◽  
Biology Research

Light microscopy has long been an indispensable tool for cell biology research. From biological problems to biological knowledge, there are two more critical links in the light microscopy approach: labeling and quantitative analysis. Therefore, an integrative approach is desirable in order to deal with practical challenges in biological light microscopy.

On the stochastic properties of bursts of single ion channel openings and of clusters of bursts

1982 ◽  
Vol 300 (1098) ◽  
pp. 1-59 ◽  
Keyword(s):  
Steady State ◽  
Ion Channels ◽  
Computer Program ◽  
Ion Channel ◽  
Energy Supply ◽  
Single Channel ◽  
Transition Probabilities ◽  
Transition Rates ◽  
Open Time ◽  
Stochastic Properties

Characteristics of observed bursts of single channel openings were derived recently for two particular ion channel mechanisms. In this paper these methods are generalized so that the observable characteristics of bursts can be calculated directly for any mechanism that has transition probabilities that are independent of time as long as the process is at equilibrium or is maintained in a steady state by an energy supply. General expressions are given for the distributions of the open time, the number of openings per burst, the total open time per burst, the gaps within and between bursts, and so on. With the aid of these general results a single computer program can be written that will provide numerical values for such distributions for postulated mechanism, given only the transition rates between the various states. The results are illustrated by a numerical example of a mechanism in which two agonist molecules can bind sequentially, and either singly or doubly occupied receptor ion channels may open. The analogous theory is also given for the case where bursts of channel openings are grouped into clusters; many of the results bear a close analogy with those found for simple bursts.

Ion homeostasis, channels, and transporters: an update on cellular mechanisms

2004 ◽  
Vol 28 (4) ◽  
pp. 143-154 ◽  
Author(s):  
George R. Dubyak
Keyword(s):  
Ion Channels ◽  
Subcellular Localization ◽  
Ion Transport ◽  
Membrane Transport ◽  
Cell Biology ◽  
Functional Characterization ◽  
Transport Proteins ◽  
Transport Protein ◽  
Membrane Transport Proteins ◽  
Functional Analyses

The steady-state maintenance of highly asymmetric concentrations of the major inorganic cations and anions is a major function of both plasma membranes and the membranes of intracellular organelles. Homeostatic regulation of these ionic gradients is critical for most functions. Due to their charge, the movements of ions across biological membranes necessarily involves facilitation by intrinsic membrane transport proteins. The functional characterization and categorization of membrane transport proteins was a major focus of cell physiological research from the 1950s through the 1980s. On the basis of these functional analyses, ion transport proteins were broadly divided into two classes: channels and carrier-type transporters (which include exchangers, cotransporters, and ATP-driven ion pumps). Beginning in the mid-1980s, these functional analyses of ion transport and homeostasis were complemented by the cloning of genes encoding many ion channels and transporter proteins. Comparison of the predicted primary amino acid sequences and structures of functionally similar ion transport proteins facilitated their grouping within families and superfamilies of structurally related membrane proteins. Postgenomics research in ion transport biology increasingly involves two powerful approaches. One involves elucidation of the molecular structures, at the atomic level in some cases, of model ion transport proteins. The second uses the tools of cell biology to explore the cell-specific function or subcellular localization of ion transport proteins. This review will describe how these approaches have provided new, and sometimes surprising, insights regarding four major questions in current ion transporter research. 1) What are the fundamental differences between ion channels and ion transporters? 2) How does the interaction of an ion transport protein with so-called adapter proteins affect its subcellular localization or regulation by various intracellular signal transduction pathways? 3) How does the specific lipid composition of the local membrane microenvironment modulate the function of an ion transport protein? 4) How can the basic functional properties of a ubiquitously expressed ion transport protein vary depending on the cell type in which it is expressed?

Absence of mitochondrial activation during levosimendan inotropic action in perfused paced guinea pig hearts as demonstrated by modular control analysis

2010 ◽  
Vol 299 (3) ◽  
pp. R786-R792 ◽  
Author(s):  
Véronique Deschodt-Arsac ◽  
Guillaume Calmettes ◽  
Gérard Raffard ◽  
Philippe Massot ◽  
Jean-Michel Franconi ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Guinea Pig ◽  
Energy Supply ◽  
Cardiac Contraction ◽  
Integrative Approach ◽  
Energetic Efficiency ◽  
Control Analysis ◽  
Inotropic Action ◽  
Inotropic Effects ◽  
Modular Control

Levosimendan is a calcium sensitizer developed for the treatment of heart failure. It increases contractile force by enhancing the sensitivity of myofilaments to calcium. Besides this sensitizing effect, the drug has also been reported to show some inhibitory action on phosphodiesterase 3 (PDE3). The inotropic effects of levosimendan have been studied on guinea pig paced perfused hearts by using modular control analysis (MoCA) (Diolez P, Deschodt-Arsac V, Raffard G, Simon C, Santos PD, Thiaudiere E, Arsac L, Franconi JM. Am J Physiol Regul Integr Comp Physiol 293: R13–R19, 2007.), an integrative approach of heart energetics using noninvasive 31P NMR. The aim was to evaluate quantitatively the respective effects of this drug on energy supply and demand modules. Under our experimental conditions, 0.7 μM levosimendan induced a 45% increase in paced heart output associated with a 7% decrease in phosphocreatine and a negligible increase in oxygen consumption. Because MoCA allows in situ study of the internal regulations in intact beating heart energetics, it was applied to describe quantitatively by which routes levosimendan exerts its inotropic action. MoCA demonstrated the absence of any significant effect of the drug on the supply module, which is responsible for the lower increase in oxygen consumption, compared with epinephrine, which increases the ratio between myocardial oxygen consumption and cardiac contraction. This result evidences that, under our conditions, a possible effect of levosimendan on PDE3 activity and/or intracellular calcium remains very low on mitochondrial activity and insignificant on integrated cardiac energetics. Thus, levosimendan inotropic effect on guinea pig heart depends almost entirely on the calcium-sensitizing properties leading to myofilament activation and the concomitant activation of energy supply by the decrease in PCr, therefore improving energetic efficiency of contraction.

Molecular identification of PAL-E, a widely used endothelial-cell marker

Blood ◽  
2005 ◽  
Vol 106 (10) ◽  
pp. 3405-3409 ◽  
Author(s):  
Harri Niemelä ◽  
Kati Elima ◽  
Tiina Henttinen ◽  
Heikki Irjala ◽  
Marko Salmi ◽  
...  
Keyword(s):  
Molecular Identification ◽  
Vascular Endothelial Cells ◽  
Specific Marker ◽  
Vascular Endothelial ◽  
Lymphatic Endothelium ◽  
Cell Marker ◽  
Molecular Identity ◽  
Endothelial Cell Marker ◽  
Fenestrated Endothelium ◽  
Pathologische Anatomie

Abstract The pathologische anatomie Leiden-endothelium (PAL-E) antibody has been used for almost 20 years as a specific marker for vascular endothelial cells. Due to the fact that this antibody works only in very limited applications, the molecular identity of PAL-E has remained unknown. In this work, we demonstrate by double stainings, cross-immunoprecipitations, and transfectants that the PAL-E antigen is identical with a protein designated PV-1 (plasmalemmal vesicle 1) or FELS (fenestrated endothelial-linked structure protein) and is not vimentin, as reported earlier. As the expression of this molecule is by no means restricted to fenestrated endothelium, we suggest the use of the name PLVAP for this protein. Molecular identification of PLVAP should help in the production of new tools for the identification of vascular as opposed to lymphatic endothelium and to elucidate the function of this protein.

scholarly journals Bone Morphogenetic Protein 4 Signalling in Neural Stem and Progenitor Cells during Development and after Injury

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Alistair E. Cole ◽  
Simon S. Murray ◽  
Junhua Xiao
Keyword(s):  
Glial Cell ◽  
Bone Morphogenetic Proteins ◽  
Cell Biology ◽  
Cell Development ◽  
Cns Injury ◽  
Morphogenetic Protein ◽  
Stem And Progenitor Cells ◽  
Substantial Progress ◽  
The Central Nervous System ◽  
Extracellular Signalling

Substantial progress has been made in identifying the extracellular signalling pathways that regulate neural stem and precursor cell biology in the central nervous system (CNS). The bone morphogenetic proteins (BMPs), in particular BMP4, are key players regulating neuronal and glial cell development from neural precursor cells in the embryonic, postnatal, and injured CNS. Here we review recent studies on BMP4 signalling in the generation of neurons, astrocytes, and oligodendroglial cells in the CNS. We also discuss putative mechanisms that BMP4 may utilise to influence glial cell development following CNS injury and highlight some questions for further research.

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