Techniques and applications of extracellular space determination in mammalian tissues

This review summarizes the ways in which the extracellular space (ECS) may be estimated in mammalian tissues, and briefly describes some of the uses to which the EC confinement of certain molecules (markers or tracers) may be put in the elucidation of physiological functions. The introductory section is followed by a description of the more commonly used marker molecules and their functional characteristics, and of factors likely to lead to the spurious over- or under-estimation of the ECS. Certain alternative methods are also described, in particular those based on morphological and electrical criteria which seek to demonstrate small, functionally important, changes in the size of specialized regions of the ECS (e.g. lateral cellular interspaces) without necessarily being required to provide a quantitatively precise estimate of their size. Section III describes the results of measurements of ECS in various mammalian tissues (muscle, gastro-intestinal tract, nervous tissue, crystalline lens, placenta, lung and kidney) and some applications of EC markers to investigation of cellular function (e.g. uptake of metabolic substrates and epithelial transport) and, in outline, characterization of capillary permeability. The available literature in this field is very extensive, and in the interests of brevity the reader is, where appropriate, referred to previous reviews covering specialized aspects of ECS determination and related topics.