scholarly journals The Role of Microglia Membrane Potential in Chemotaxis

2020 ◽  
Author(s):  
Laura Laprell ◽  
Christian Schulze ◽  
Marie-Luise Brehme ◽  
Thomas G. Oertner

Abstract Microglia react to danger signals by rapid and targeted extension of cellular processes towards the source of the signal. This positive chemotactic response is accompanied by a hyperpolarization of the microglia membrane. Here we show that optogenetic depolarization of microglia has little effect on baseline motility, but significantly slows down the chemotactic response. Reducing the extracellular Ca2+ concentration mimics the effect of optogenetic depolarization. As the membrane potential sets the driving force for Ca2+ entry, hyperpolarization is an integral part of rapid stimulus-response coupling in microglia. Compared to typical excitable cells such as neurons, the sign of the activating response is inverted in microglia, leading to inhibition by depolarizing channelrhodopsins.

2020 ◽  
Author(s):  
Laura Laprell ◽  
Christian Schulze ◽  
Marie-Luise Brehme ◽  
Thomas G. Oertner

AbstractMicroglia react to danger signals by rapid and targeted extension of cellular processes towards the source of the signal. This positive chemotactic response is accompanied by a hyperpolarization of the microglia membrane. Here we show that optogenetic depolarization of microglia has little effect on baseline motility, but significantly slows down the chemotactic response. Reducing the extracellular Ca2+ concentration mimics the effect of optogenetic depolarization. As the membrane potential sets the driving force for Ca2+ entry, hyperpolarization is an integral part of rapid stimulus-response coupling in microglia. Compared to typical excitable cells such as neurons, the sign of the activating response is inverted in microglia, leading to inhibition by depolarizing channelrhodopsins.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Laura Laprell ◽  
Christian Schulze ◽  
Marie-Luise Brehme ◽  
Thomas G. Oertner

AbstractMicroglia react to danger signals by rapid and targeted extension of cellular processes towards the source of the signal. This positive chemotactic response is accompanied by a hyperpolarization of the microglia membrane. Here, we show that optogenetic depolarization of microglia has little effect on baseline motility, but significantly slows down the chemotactic response. Reducing the extracellular Ca2+ concentration mimics the effect of optogenetic depolarization. As the membrane potential sets the driving force for Ca2+ entry, hyperpolarization is an integral part of rapid stimulus-response coupling in microglia. Compared to typical excitable cells such as neurons, the sign of the activating response is inverted in microglia, leading to inhibition by depolarizing channelrhodopsins.


2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Julieta Aprea ◽  
Federico Calegari

The concerted action of ion channels and pumps establishing a resting membrane potential has been most thoroughly studied in the context of excitable cells, most notably neurons, but emerging evidences indicate that they are also involved in controlling proliferation and differentiation of nonexcitable somatic stem cells. The importance of understanding stem cell contribution to tissue formation during embryonic development, adult homeostasis, and regeneration in disease has prompted many groups to study and manipulate the membrane potential of stem cells in a variety of systems. In this paper we aimed at summarizing the current knowledge on the role of ion channels and pumps in the context of mammalian corticogenesis with particular emphasis on their contribution to the switch of neural stem cells from proliferation to differentiation and generation of more committed progenitors and neurons, whose lineage during brain development has been recently elucidated.


2005 ◽  
Vol 93 (3) ◽  
pp. 1557-1568 ◽  
Author(s):  
Lei Zhu ◽  
David Lovinger ◽  
Eric Delpire

As excitable cells, neurons experience constant changes in their membrane potential due to ion flux through plasma membrane channels. They maintain their transmembrane cation concentrations through robust Na+/K+-ATPase pump activity. During synaptic transmission and spread of action potentials, the concentration of the major anion, Cl−, is also under constant challenge from membrane potential changes. Moreover, intracellular Cl− is also affected by ligand-gated Cl− channels such as GABAA and glycine receptors. To regulate intracellular Cl− in an electrically silent manner, neurons couple the movement of Cl− with K+. In this study, we have used gene-targeted KCC2−/− mice to provide strong evidence that KCC2, the neuronal-specific K-Cl co-transporter, drives neuronal Cl− to low concentrations, shifting the GABA reversal potential toward more negative potentials, thus promoting hyperpolarizing GABA responses. Cortical neurons lacking KCC2, not only fail to show a developmental decrease in [Cl−]i, but also are unable to regulate [Cl−]i on Cl− loading or maintain [Cl]i during membrane depolarization. These data are consistent with the central role of KCC2 in promoting inhibition and preventing hyperexcitability.


1997 ◽  
Vol 272 (1) ◽  
pp. L78-L84 ◽  
Author(s):  
S. I. Zharikov ◽  
H. Herrera ◽  
E. R. Block

System y+ accounts for the majority of L-arginine transport by pulmonary artery endothelial cells (PAEC). Given that membrane potential is a driving force for transport via system y+, we examined the hypothesis that hypoxia inhibits this transport by decreasing membrane potential. Porcine PAEC or plasma membrane vesicles derived from these cells were exposed to normoxia (room air-5% CO2) or hypoxia (0% O2-95% N2-5% CO2). After exposure, L-[3H]arginine transport and/or accumulation of the lipophilic cation [3H]tetraphenylphosphonium, a quantitative sensor of changes in cell membrane potential, were measured. Hypoxia caused reversible time-dependent decrease in L-arginine transport and membrane potential in PAEC and in plasma membrane vesicles. Comparable decreases in membrane potential and L-arginine transport by PAEC were also observed after depolarization induced by KCl or ouabain. Hyperpolarization, induced by valinomycin, increased membrane potential and L-arginine transport in PAEC and plasma membrane vesicles. Valinomycin also prevented the hypoxia-mediated decreases in membrane potential and L-arginine transport in PAEC. These results indicate that hypoxia-induced plasma membrane depolarization is responsible for reduced L-arginine transport by system y+ in hypoxic porcine PAEC.


1987 ◽  
Author(s):  
A Yamaguchi ◽  
H Azuma ◽  
S Sekizaki ◽  
K Tanoue ◽  
H Yamazaki

Though membrane depolarization is an imoportant step in signal transduction in living cells, it is immpossible to use microelectrode for analyses of the phenomenon in platelets due to the size limitation. Cetiedil, oc-cyclohexyl�3�thiophenacetic acid 2-(hexahydro-1H-azep in-1-yl) ester, is the drug which inhibits erythrocyte sickling by promoting net salt and water gain. It increases flux of both Na and K, and net Na gain exceeds net K loss. We used cetiedil as a tool to modify intracellular Na and K contents which are closely related to membrane potential.Normal human platelets contained 23.5±3.7 nEq of Na and 82.7±5.6 nEq of K per 108 platelets measured by atomic absorption spectrophotometer (n=6, meantSE). When 0.5 µ/ml of thrombin was added, Na content increased to 200 % and K content decreased to 80% of the resting value after 15 sec. 22 Na spaces of platelets (0.3L±0.07 µl/l0° platelets in the resting stage, n=4) increased to 0.53±0.12 at 2 min after thrombin. After 5 min incubation with 50 µM cetiedil, Na contents increased and K contents decreased slightly. Under the cetiedil treatment, the increase in Na and decrease in K contents induced by thrombin were inhibited significantly. The increase in 22 Na spaces induced by thrombin was also inhibited. Thrombin-induced membrane depolarization measured by membrane potential probe dye, diS, also was inhibited by cetiedil. In the presence of 50 yM cetiedil, magnitude of depolarization was 27.6±1.0 mV (n=30). The depolarization was not affected by Na transport inhibitors, such as procaine and tetrodotoxine, but inhibited by low Na content in the suspension medium. Cetiedil also inhibited platelet aggregation and TXA2 synthesis by thrombin. However, the treatment did not induce any changes in platelet volume, their morphology under elecrton microscope, Ca content and LDH leakage. There is a concept that a small degree of depolarization can inhibit the stimulus-response coupling of various kinds of cells. A similar mechanism might be present in platelet membrane. A role of membrane depolarization in platelet activation is suggested


2006 ◽  
pp. 20-37 ◽  
Author(s):  
M. Ershov

The economic growth, which is underway in Russia, raises new questions to be addressed. How to improve the quality of growth, increasing the role of new competitive sectors and transforming them into the driving force of growth? How can progressive structural changes be implemented without hampering the rate of growth in general? What are the main external and internal risks, which may undermine positive trends of development? The author looks upon financial, monetary and foreign exchange aspects of the problem and comes up with some suggestions on how to make growth more competitive and sustainable.


2011 ◽  
Vol 162 (7) ◽  
pp. 209-215
Author(s):  
Jean-François Métraux

In the years since 2000, the authorities in charge of forests in canton Vaud have made some substantial changes as a reaction to the political decisions arising from the Swiss Forest Programme and the projected revision of the Federal forestry Law, as well as to the deterioration of the economic situation in forestry enterprises. This article gives a survey of the directions taken. Thus the canton recognises the primordial role of wood production as a driving force behind the creation of a multifunctional forest. The Service for Forests, Wildlife and Nature has invested a great deal in planning, and has redefined the management plan to be an instrument intended for forest owners and forest managers. The canton has innovated by introducing forestry groups and a scheme of equalisation of forestry costs between communes. Hence the conception of forestry management in canton Vaud is resolutely that of a multifunctional natural heritage.


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