Events

CATION CATASTROPHE: CHOICES AND CONSEQUENCES IN MODELING SINGLE NEURON DEPOLARIZATION

Abstract

Spreading depression (SD) is a phenomenon associated with neuronal depolarization, massive re-distribution of ions and cytotoxic cell swelling. Waves of SD put enormous metabolic strain on brain tissue and are thus associated with delayed cell death and function loss. One approach to find a therapeutic target for SD prevention is to capture the necessary and sufficient processes that can mimic the observed behavior in a mathematical model.

Several ion-based single cell models with Hodgkin-Huxley dynamics have been published that can exhibit a transient depolarization, thought to be the cellular correlate of SD. However, some constraints and assumptions in these models are in our view not (bio)physically admissible. We aimed to develop such a model that is simple, has volume dynamics and also obeys the (bio)physical constraint of bulk electroneutrality. In silico experiments were conducted to assess if such a single cell can produce a transient depolarization and if diffusion of K+, Na+ and Cl− is sufficient to spread depolarization from cell to cell.

Our conclusion is that the current model is insufficient to explain cell-to-cell progression of spreading depolarization. Furthermore, once the sodium content of the system is allowed to vary, a second stable but depolarized equilibrium emerges at physiological pumping strengths. These results indicate that additional dynamics or limitations are necessary to explain transient depolarization. In addition, they signal a need for further experimental validation of widely used modeling assumptions.

Wednesday 1 April 2015, 16:00 h

Building Carré 2L