The extracellular space of a tissue is tempting to ignore; after all it is connected to the bathing solution and substances in the bath can “freely diffuse” through the extracellular space and reach the membranes of the cells. Historically, workers in many tissues have succumbed to temptation, ignored extracellular space, and eventually realized that they had ignored an important determinant of experimental results and (presumably) physiological function. The historical path to the investigation of the extracellular space, although well trodden, has had different names in different fields, or should I say gardens. In the study of axons, the relevant extracellular space is called “the Frankenhaeuser-Hodgkin space.”’.* In skeletal muscle it is the lumen of the in cardiac muscle the spaces are the lumen of the tubules and the clefts between cells? In epithelia it is both the lateral intercellular spaces and the “unstirred” layers of the serosal and mucosal faces of the tissue (see Clausen et al.’ and references there). The multiplicity of names for the same historical path (and logical phenomena) has hidden the identity of the physical and physiological processes. This paper will try to place the study of the extracellular space of the brain in the context of earlier work. The extracellular space of many tissues restricts movement because it is tortuous and narrow, with a long path length for diffusion and a large ratio of membrane surface to extracellular volume. In these circumstances properties of the tissue are not entirely set by their membranes, channels, and transport systems. Rather the extracellular space becomes a significant impediment to, and thus determinant of, flow. In each tissue, there are two main classes of effects of the restricted extracellular space: the changes in local concentrations (i.e., chemical potential) of ions and the change in local concentration of net electrical charge (i.e., voltage or electrical potential) caused by the resistance of the extracellular space. A similar approach has been taken in the analysis of the flow of water by Mathias, and the same theme is heard there: the extracellular space plays an important role in controlling the flow of water. The physiological .analysis of the role of the extracellular space presupposes a qualitative and quantitative knowledge of the structure of the tissue. Thus, serious physiological work in this field must be accompanied by anatomical analysis: one must know the topology, the connectivity, and the extent of the extracellular space before one can analyze it. The techniques of electron microscopy allow a reasonably straightforward analysis of the topology of the extracellular space. Artifacts rarely change the connectivity of
[1]
Vimal Singh,et al.
Perturbation methods
,
1991
.
[2]
R. Kline,et al.
Extracellular calcium ion depletion in frog cardiac ventricular muscle.
,
1985,
Biophysical journal.
[3]
J. Vergara,et al.
Dichroic behavior of the absorbance signals from dyes NK2367 and WW375 in skeletal muscle fibers
,
1984,
The Journal of general physiology.
[4]
S A Lewis,et al.
Impedance analysis of a tight epithelium using a distributed resistance model.
,
1979,
Biophysical journal.
[5]
R. Eisenberg,et al.
Measurement of the impedance of frog skeletal muscle fibers.
,
1974,
Biophysical journal.
[6]
R. Eisenberg,et al.
Circuit Models of the Passive Electrical Properties of Frog Skeletal Muscle Fibers
,
1974,
The Journal of general physiology.
[7]
R. Eisenberg,et al.
Impedance of Frog Skeletal Muscle Fibers in Various Solutions
,
1974,
The Journal of general physiology.
[8]
A. Hodgkin,et al.
The after‐effects of impulses in the giant nerve fibres of Loligo
,
1956,
The Journal of physiology.
[9]
R. Mathias.
Analysis of Membrane Properties Using Extrinsic Noise
,
1984
.
[10]
R. Eisenberg,et al.
Structural analysis of electrical properties of cells and tissues.
,
1980,
Critical reviews in bioengineering.
[11]
E. Weibel.
Stereological Methods. Practical methods for biological morphometry
,
1979
.
[12]
R. Eisenberg,et al.
Electrical properties of spherical syncytia.
,
1979,
Biophysical journal.
[13]
D. Attwell,et al.
The voltage clamp of multicellular preparations.
,
1977,
Progress in biophysics and molecular biology.
[14]
R. Eisenberg,et al.
Electrical properties of frog skeletal muscle fibers interpreted with a mesh model of the tubular system.
,
1977,
Biophysical journal.
[15]
R. Eisenberg,et al.
Interpretation of some microelectrode measurements of electrical properties of cells.
,
1973,
Annual review of biophysics and bioengineering.
[16]
R. Eisenberg,et al.
Three-dimensional electrical field problems in physiology
,
1970
.