When they become simultaneously leaky to both Na and Cl, excitable cells are vulnerable to potentially lethal cytotoxic swelling. Swelling ensues in spite of an isosmotic milieu because the entering ions add osmolytes to the cytoplasm's high concentration of impermeant anionic osmolytes. An influx of osmotically-obliged water is unavoidable. A cell that cannot stanch at least one the leaks will succumb to death by Donnan effect. "Sick excitable cells" are those injured through ischemia, trauma, inflammation, hyperactivity, genetically-impaired membrane skeletons and other insults, all of which foster bleb-damage to regions of the plasma membrane. Nav channels resident in damaged membrane exhibit left-shifted kinetics; the corresponding Nav window conductance constitutes a Na-leak. In cortical neurons, sustained depolarization to ∼-20mV elicits a sustained lethal gCl. Underlying V in skeletal muscle is a constitutively active gCl; not surprisingly therefore, dystrophic muscle fibers, which are prone to bleb damage and which exhibit Nav-leak and Na-overload, are prone to cytotoxic swelling. To restore viability in cytotoxically swelling neurons and muscle, the imperative of fully functional ion homeostasis is well-recognized. However, as emphasized here, in a healthy excitable cell, fully functional membrane tension homeostasis is also imperative. ATPase-pumps keep plasma membrane batteries charged, and ATPase-motor proteins maintain membrane tone. In sick excitable cells, neither condition prevails.
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http://dx.doi.org/10.1016/bs.ctm.2018.06.001 | DOI Listing |
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