Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.20.391813v1?rss=1 Authors: Joos, B., Morris, C. E. Abstract: 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. Copy rights belong to original authors. Visit the link for more info