Ion fluxes, transmembrane potential, and osmotic stabilization: a new dynamic electrophysiological model for eukaryotic cells

Abstract

Survival of mammalian cells is achieved by tight control of cell volume, while transmembrane potential has been known to control many cellular functions since the seminal work of Hodgkin and Huxley. Regulation of cell volume and transmembrane potential have a wide range of implications in physiology, from neurological and cardiac disorders to cancer and muscle fatigue. Therefore, understanding the relationship between transmembrane potential, ion fluxes, and cell volume regulation has become of great interest. In this paper we derive a system of differential equations that links transmembrane potential, ionic concentrations, and cell volume. In particular, we describe the dynamics of the cell within a few seconds after an osmotic stress, which cannot be done by the previous models in which either cell volume was constant or osmotic regulation instantaneous. This new model demonstrates that both membrane potential and cell volume stabilization occur within tens of seconds of changes in extracellular osmotic pressure. When the extracellular osmotic pressure is constant, the cell volume varies as a function of transmembrane potential and ion fluxes, thus providing an implicit link between transmembrane potential and cell volume. Experimental data provide results that corroborate the numerical simulations of the model in terms of time-related changes in cell volume and dynamics of the phenomena. This paper can be seen as a generalization of previous electrophysiological results, since under restrictive conditions they can be derived from our model.

Numerical study on the effect of capacitively coupled electrical stimulation on biological cells considering model uncertainties

“…A great contribution would be a clarification of the question whether voltage-gated 7 or other channels are involved in the signal transduction. This could lead to multiphysics models including, for example, ion dynamics 66 or the mechanical behavior of the membrane 53 , 67 . Furthermore, the adhesion of chondrocytes and resulting gaps between cell membrane and insulator should be investigated to provide reliable geometric models of cells in capacitive-coupling stimulation chambers.…”

Osmotic behaviour of human mesenchymal stem cells: Implications for cryopreservation

“…Far from being explanatory, the above-mentioned conceptual framework suggests the activation of control mechanisms for cell volume excursions not considered in the 2-parameter model. Borrowing from available literature, intracellular mechanisms involving ion-pumps and/or ion-channels could represent a possible candidate for explaining the observed osmotic behaviour [ 41 – 43 ]. However, it is worth noting that ion pumps work on relatively long time scales, not compatible with the rapid response to osmosis exhibited by hMSCs.…”

Cell Volume Regulation in Cultured Human Retinal Müller Cells Is Associated with Changes in Transmembrane Potential

“…To achieve a stationary condition, passive ion fluxes are assumed to be compensated by opposing active fluxes that do not balance those generated during RVD. Active fluxes were assumed to be constant since several previous reports demonstrated that short-term volume regulation is not affected by them [25], [26].…”