1. A technique is described for recording the bioelectric activity of the squid giant axon during and following alteration of the internal axonal composition with respect to ions or other substances.

2. Experimental evidence indicates that the technique as described is capable of measuring changes in local bioelectric activity with an accuracy of 10 to 15 per cent or higher.

3. Alterations of the internal K+ or Cl- concentrations do not cause the change in resting potential expected on the basis of a Donnan mechanism.

4. The general effect of microinjection of K+ Rb+, Na+, Li+, Ba++, Ca++, Mg++, or Sr++ is to cause decrease in spike amplitude, followed by propagation block.

5. The resting potential decreases when the amplitude of the spike becomes low and block is incipient.

6. The decrease in resting potential and spike amplitude may be confined to the immediate vicinity of the injection.

7. At block, the resting potential decreases up to 50 per cent, but injection of small quantities of divalent cations may cause much larger localized depolarization.

8. The blocking effectiveness of K+, Na+, and Ca++ expressed as reciprocals of the relative amounts needed to cause block is approximately 1:5:100. Rb+ has the same low effectiveness as does K+. Li+ resembles Na+. Ba++ and Mg++ are approximately as effective as Ca++.

9. Microinjection of Na+ may cause marked prolongation of the spike at the injection site as well as decrease in its amplitude.

10. The anions used (Cl-, HCO3-, NO3-, SO4-, aspartate, and glutamate) do not seem to exert specific effects.

11. A tentative explanation is offered for the insensitivity of the resting potential to changes in the axonal ionic composition.

12. New data are presented on the range of variation, in a large sample, of the magnitude of the resting potential and spike amplitude.

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