The requirement for calcium ions and the effect of other ions on axoplasmic transport in mammalian nerve.

1. Until recently it was believed that axoplasmic transport in vitro was not affected by Ca2+, transport being normal in Ca2+-free medium. This was found due to the presence of the relatively impermeable perineurial sheath around the nerve trunks. Using a desheathed cat peroneal nerve preparation, axoplasmic transport was shown to require an adequate level of Ca2+ in the external medium. In a buffered Ca2+-free medium, transport began to decline within 30 min and a complete block occurred in 2 . 6 hr. A concentration of 5 mM-Ca2+ added to a buffered isotonic sucrose of NaCl solution was able to maintain transport. With lower concentrations of Ca2+ of 1 . 5-3 . 0 mM, those usually present in the extracellular fluid or in a Ringer medium, some impairment of transport was seen but the addition of 4 mM-K+ restored the normal pattern of axoplasmic transport. With Ca2+ concentrations below 0 . 75 mM, however, 4 mM-K+ was unable to sustain transport. 2. Potassium by itself at a concentration of 4 mM when added to a buffered isotonic sucrose of NaCl medium was unable to prolong the time of transport block beyond that seen in buffered isotonic NaCl or sucrose solutions. In concentrations of K+ up to 25 mM, 1 . 5-5 mM-Ca2+ was required for normal transport. With moderately higher concentrations of K+ in the range of 50-100 mM, normal appearing transport was seen with or without Ca2+. This was seen whether or not Na+ was present in the medium. At higher levels of K+, 120-150 mM, decreased transport was seen, with or without the addition of either 15 mM-Na+ or Ca2+ in concentrations of 1 . 5-3 . 0 mM. 3. While Mg2+ could not substitute completely for Ca2+ in maintaining transport, it was able to prolong the time before block occurred. An extra 30-60 min of downflow was seen when 5 mM-Mg2+ was added to a buffered isotonic NaCl medium. Magnesium also acts synergistically with Ca2+. Concentration of Ca2+ as low as 0 . 25 mM was, with the addition of 1 . 5 mM-Mg2+, able to maintain transport. 4. The results are interpreted in the light of studies of the mechanism of Ca2+ regulation known to occur in giant nerve fibres and other clls controlling the level of free Ca2+. The relationship of Ca2+ to the mechanism considered to underlie axoplasmic transport in nerve fibres is also discussed.