The effect of graded hypertonia on interstitial volume, tissue resistance and synaptic transmission in rat hippocampal tissue slices.

Rat hippocampal slices were exposed for 30 min to each of three levels of increased osmolarity (pi o), achieved by adding 25, 50 or 100 mM mannitol to the bathing solution. The interstitial volume (ISV) determined as the relative volume of dilution of the probe ion, tetra-methyl-ammonium (TMA+), increased markedly, indicating cell shrinkage. Tissue resistance (Ro) decreased only slightly with increasing pi o. The discrepancy between ISV increase and Ro decrease suggests increased electrical resistance of cell membranes. TMA+ dilution appears to be a more reliable measure of ISV than is Ro. During recovery from hypertonic treatment the previously expanded ISV frequently shrank, suggesting post-hypertonic cell swelling. Hypertonic treatment significantly depressed orthodromically transmitted population spikes and extracellular synaptic potentials (fEPSPs), and the degree of depression varied with the increase in pi o. Changing recording condition due to reduced Ro could not account for the depression of population spikes and fEPSPs. Following return to normal pi o, orthodromic population spikes frequently overshot initial control amplitude. An isolated episode of spreading depression occurred in about half of the slices following exposure to the most severely hypertonic solution. At the end of 2.5 h recovery, orthodromic spikes did not significantly differ from those of untreated control slices observed for the same length of time. We conclude that synaptic transmission is depressed by elevation of pi o, and the depression is concentration dependent and reversible.