Diffusion in slice preparations bathed in unstirred solutions.

A diffusion model is described here, which allows for the estimations of drug concentration changes in porous media, such as in slice tissues of the central nervous system (CNS) bathed in unstirred solutions following abrupt changes of drug concentration. This model may be used for the interpretation of data obtained in neuropharmacological studies if (i) the diffusion coefficient of the molecules under investigation is constant within the excised tissue, (ii) drug molecules are diffusing only in the extracellular space (ECS) and are not bound by the tissue, (iii) drug molecules diffuse mainly within one dimension, (iv) the drug concentration in the bath is changed within 5 s, and (v) the bathing solutions at the surfaces of the slices are stagnant during the period of diffusion. To test this model, estimated tetramethylammonium (TMA) ion concentrations within a tissue slice were compared to actual TMA concentration changes measured at the same depth in the tissue of hippocampal slices by means of TMA-sensitive microelectrodes. A statistically significant correlation (P less than 0.05) was observed between the estimated and measured TMA concentrations which indicates that the model is valid under the defined conditions.