Cytotoxic Swelling of Sick Excitable Cells – Impaired Ion Homeostasis and Membrane Tension Homeostasis in Muscle and Neuron

Morris, Catherine E.

doi:10.1016/bs.ctm.2018.06.001

Cited by 9 publications

(12 citation statements)

References 120 publications

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“…245–267) and other investigators (Dai & Sheetz, 1999; Dai et al, 1997, 1998; Groulx et al, 2006; Raucher & Sheetz, 1999; Sens & Turner, 2006; Sinha et al, 2011), showing that there are significant membrane reservoirs in membrane folds and invaginations, which may accommodate an increase in cell volume and apparent increase in cell surface area without any membrane stretch, thus buffering membrane tension. Indeed, Morris (Morris, 2018) describes the concept of “membrane tension homeostasis” (MTH) as an essential process that works to prevent cellular plasma membranes from lysing under osmotic stress by employing a combination of multiple passive and active stochastic tension modulating steps to resist rupture.…”

Section: Membrane Tensionmentioning

confidence: 99%

Membrane Stiffening in Osmotic Swelling

Ayee

Levitan

2018

Cell Volume Regulation

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The effects of osmotic swelling on key cellular biomechanical properties are explored in this chapter. We present the governing equations and theoretical backgrounds of the models employed to estimate cell membrane tension and elastic moduli from experimental methods, and provide a summary of the prevailing experimental approaches used to obtain these biomechanical parameters. A detailed analysis of the current evidence of the effects of osmotic swelling on membrane tension and elastic moduli is provided. Briefly, due to the buffering effect of unfolding membrane reservoirs, mild hypotonic swelling does not change membrane tension or the adhesion of the membrane to the underlying cytoskeleton. Conversely, osmotic swelling causes the cell membrane envelope to stiffen, measured as an increase in the membrane elastic modulus.

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Section: Membrane Tensionmentioning

confidence: 99%

Membrane Stiffening in Osmotic Swelling

Ayee

Levitan

2018

Cell Volume Regulation

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“…SM-CD can now only return to a physiological steady-state ( Figure Sup02 Ci,ii,iii ) if it up-regulates its pump-strength (=↑↑hyperpolarizing I maxpump ) enough to repolarize itself to a different unstable threshold (→more ectopic firing) from which (post-APs) it repolarizes to a physiological steady-state. This bistable two-thresholds scenario (“ion homeostatic excitability”) is a feature of excitable P-L/D systems (Hubel et al 2014; Morris 2018).…”

Section: Resultsmentioning

confidence: 99%

“…If it had SA=1885 µm 2 plus a slack 115 µm 2 for passive tension-buffering (1.06-fold swelling) that would be 2000 µm 2 encircling 14,137 µm 3 . (Sarcolemma’s dynamic tension-buffering (Sinha et al 2011; Lo et al 2016; Morris 2018) is not modeled here). A SM-CD unit such as this would be serving ∼1 myonuclear domain.…”

Section: Discussionmentioning

confidence: 99%

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The Pump-Leak/Donnan ion homeostasis strategies of skeletal muscle fibers and neurons

Joós

Morris

2020

Preprint

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Skeletal muscle fibers (SMFs) and neurons are low and high duty-cycle excitable cells constituting exceptionally large and extraordinarily small fractions of vertebrate bodies. The immense ClC-1-based chloride-permeability (PCl) of SMFs has thwarted understanding of their Pump-Leak/Donnan (P-L/D) ion homeostasis. After formally defining P-L/D set-points and feedbacks, we therefore devise a simple yet demonstrably realistic model for SMFs. Hyper-stimulated, it approximates rodent fibers’ ouabain-sensitive ATP-consumption. Size-matched neuron-model/SMF-model comparisons reveal steady-states occupying two ends of an energetics/resilience P-L/D continuum. Excitable neurons’ costly vulnerable process is Pump-Leak dominated. Electrically-reluctant SMFs’ robust low-cost process is Donnan dominated: collaboratively, Donnan effectors and [big PCl] stabilize Vrest, while SMFs’ exquisitely small PNa minimizes ATP-consumption, thus maximizing resilience. “Classic” excitable cell homeostasis ([small PCl][big INaleak]), de rigueur for electrically-agile neurons, is untenable for vertebrates’ (including humans’) major tissue. Vertebrate bodies evolved thanks to syncytially-efficient SMFs using a Donnan dominated ([big PCl][small INaleak]) ion homeostatic strategy.

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“…The increased ion permeability of membranes may contribute to enhanced spontaneous electrical activity of pacemaker cells in the heart, leading to abnormalities such as arrhythmia, impaired pumping capability, and reduced cardiac output. Furthermore, the additional sodium leak in brain cells may result in neuronal hyper-excitability [ 60 ]. The involvement of ROS in neurodegenerative diseases and aging can be partially explained by the here-described lipid-mediated mechanism.…”

Section: Discussionmentioning

confidence: 99%

Covalent modification of phosphatidylethanolamine by 4-hydroxy-2-nonenal increases sodium permeability across phospholipid bilayer membranes

Jovanović

Škulj

Pohl

et al. 2019

Free Radical Biology and Medicine

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Reactive aldehydes (RAs), such as 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE), produced by cells under conditions of oxidative stress, were shown to react with phosphatidylethanolamine (PE) in biological and artificial membranes. They form RA-PE adducts, which affect the function of membrane proteins by modifying various biophysical properties of the membrane. The ratio of protein to lipid in biological membranes is different, but can reach 0.25 in the membranes of oligodendrocytes. However, the impact of RA-PE adducts on permeability ( P ) of the neat lipid phase and molecular mechanism of their action are poorly understood. In this study, we showed that HNE increased the membrane P for ions, and in particular for sodium. This effect depended on the presence of DOPE, and was not recorded for the more toxic compound, ONE. Molecular dynamics simulations suggested that HNE-PE and ONE-PE adducts anchored different positions in the lipid bilayer, and thus changed the membrane lipid area and bilayer thickness in different ways. Sodium permeability, calculated in the presence of double HNE-PE adducts, was increased by three to four orders of magnitude when compared to P Na in adduct – free membranes. A novel mechanism by which HNE alters permeability of the lipid membrane may explain the multiple toxic or regulative effects of HNE on the function of excitable cells, such as neurons, cardiomyocytes and neurosensory cells under conditions of oxidative stress.

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Cytotoxic Swelling of Sick Excitable Cells – Impaired Ion Homeostasis and Membrane Tension Homeostasis in Muscle and Neuron

Cited by 9 publications

References 120 publications

Membrane Stiffening in Osmotic Swelling

Membrane Stiffening in Osmotic Swelling

The Pump-Leak/Donnan ion homeostasis strategies of skeletal muscle fibers and neurons

Covalent modification of phosphatidylethanolamine by 4-hydroxy-2-nonenal increases sodium permeability across phospholipid bilayer membranes

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