1. Using the electrical response of giant axons in the isolated abdominal nerve cord of the cockroach, Periplaneta americana, as an indication of the ionic composition of the fluid bathing their surfaces, it has been shown that the movement of potassium ions from the bathing medium to the extra-axonal fluid, following an increase in the external concentration of this cation, involves an appreciable degree of restriction.

2. This effect is associated with an extracellular diffusion potential, which appears to result from the more rapid penetration of potassium relative to the outward diffusion of sodium ions from the extracellular system.

3. It is suggested that the restriction of intercellular diffusion may occur in the region containing tight junctions and separate desmosomes at the inner end of the intercellular clefts which traverse the perineurium.

4. If the connectives are stretched during mounting, a more rapid depolarization of the giant axons is observed. Comparison of the calculated and the experimentally observed half-times for diffusion of potassium ions to the axon surface indicates that in these preparations the rate of movement of inorganic ions from the external medium is largely determined by the extended intercellular diffusion pathway represented by the mesaxon cleft.

5. In de-sheathed preparations penetration of potassium ions is still more rapid, an effect which is postulated to result from damage to the perineurium, and the consequent production of a shorter, intracellular diffusion channel through the glial system.

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