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First published online on May 17, 2002.
 Copyright © 2002 by The Physiological Society
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Received January 22, 2002
Accepted after revision April 24, 2002

Independence of extracellular tortuosity and volume fraction during osmotic challenge in rat neocortex

June Kume-Kick1, Tomas Mazel2, Ivan Vorisek2, Sabina Hrabetova1, Lian Tao1, and C. Nicholson1*

1 Department of Physiology and Neuroscience, NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA
2 Department of Neuroscience, 2nd Medical Faculty, Charles University and Institute of Experimental Medicine AS CR, Videnska 1083, 142 20 Prague, Czech Republic

* To whom correspondence should be addressed. E-mail: charles.nicholson{at}nyu.edu.

The structural properties of brain extracellular space (ECS) are summarised by the tortuosity ({lambda}) and the volume fraction ({alpha}). To determine if these two parameters were independent, we varied the size of the ECS by changing the NaCl content to alter osmolality of bathing media for rat cortical slices. Values of {lambda} and {alpha} were extracted from diffusion measurements using the real-time ionophoretic method with tetramethylammonium (TMA+). In normal medium (305 mosmol kg-1), the average value of {lambda} was 1.69 and of {alpha} was 0.24. Reducing osmolality to 150 mosmol kg-1, increased {lambda} to 1.86 and decreased {alpha} to 0.12. Increasing osmolality to 350 mosmol kg-1, reduced {lambda} to about 1.67 where it remained unchanged even when osmolality increased further to 500 mosmol kg-1. In contrast, {alpha} increased steadily to 0.42 as osmolality increased. Comparison with previously published experiments employing 3000 Mr dextran to measure {lambda}, showed the same behaviour as for TMA+, including the same constant {lambda} in hypertonic media but with a steeper slope in the hypotonic solutions. These data show that {lambda} and {alpha} behave differently as the ECS geometry varies. When {alpha} decreases, {lambda} increases but when {alpha} increases, {lambda} rapidly attains a constant value. A previous model allowing cellular shape to alter during osmotic challenge can account qualitatively for the plateau behaviour of {lambda}.




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