Dynamics of intracellular calcium in cultured human keratinocytes after localized cell damage

Abstract

Recovery of cultured keratinocytes after scratch damage is considered to be a wound-healing model. In this study, we observed changes in intracellular calcium concentration ( ] i remained elevated in a peripheral layer of cells around the damaged area for several minutes. This layer did not appear in calcium-free medium. When the culture was switched to calcium-free medium for 30 min immediately after scratch damage, then switched back to standard (Ca 2+ -containing) medium, the recovery ratio after 24 h was approximately 25% lower than that of the culture in standard medium throughout. We speculate that delineation of damage sites by a layer of cells with increased [Ca 2+ ] i might be part of a signalling pathway that appropriately directs the wound-healing process in epidermis.

Mathematical Modeling of Calcium Waves Induced by Mechanical Stimulation in Keratinocytes

“…It has recently been reported that a strong mechanical stimulus, enough to break the cell, causes a ring-like Ca localized pattern around the broken cell [18]. This experimental observation can also be reproduced by our model, by using an even stronger stimulus .…”

“…By the same token, the function , the ATP release due to the calcium excitation, depends not on the calcium concentration itself but on the time derivative of it. Also, following a recent experimental result [18], we further assume that when a cell is broken by a strong stimulus, a stimulant is released that induces the influx of extracellular Ca through calcium channels on the plasma membrane. These features are introduced to our mathematical model to reproduce the experimental findings of the mechanical stimulation:where …”

“…At this point the stimulant is released. We also assume that the stimulant affects the Ca level only when the extracellular calcium exists [18].…”

“…In this paper, using known biochemical and dermatological results, we introduce a mathematical model that can account for the behavior of calcium waves in keratinocytes, especially a ring-shaped pattern recently observed by Tsutsumi et al [18]. In order to compare our numerical simulations with experimental data, previous experiments are reproduced and the calcium levels are measured under several conditions.…”

Model for calcium-mediated reduction of structural fluctuations in epidermis

“…Calcium dynamics obeys the diffusion equation with decay, which accounts for experimental observations that calcium waves in the epidermis propagate only within a finite range [5,[8][9][10]. The source of calcium ions, which is represented by the δ function, is considered to be located along the upper interface z = h(x,t), according to an experimental finding that sustained calcium excitation occurs around dead cells, which might account for the calcium localization layer beneath the SC [11]. Hence, in this model, calcium dynamics is affected by the shape of the upper boundary h(x,t), which is implicitly determined by the relationship S| z=h(x,t) = 1, while the differentiation is accelerated in the regions where the calcium concentration is high.…”