Letter | Published:

The sodium channel and intracellular H+ blockage in squid axons



Sodium channels in plasma membranes can be blocked by a large variety of toxins1 and local anaesthetics2. This property, however, is not confined to relatively large molecules. For instance, extracellularly applied small ions like hydrogen may also prevent the passive transport of permeant cations across open Na+ channels3–6. A typical feature of this phenomenon3,5 is that the blocking action of hydrogen is gradually relieved by increasing the voltage applied across the membrane. Although in the frog skeletal muscle there is no clear evidence for a similar intracellular action7, we report here for the squid giant axon remarkable effects on the ionic permeability of Na+ channels when the internal perfusate contains an excess of protons. Analysing the action of low pH inside and outside the fibre in terms of a kinetic model3, we could conclude that Na+ channels in squid axons are controlled by two independent groups: one with an apparent pKa of 4.6 and the other with pKa 5.8, the former feeling one-fifth of the applied membrane potential, the latter three-quarters. As with pharmacological agents8, we also show that the voltage-dependence of the H+ blockage is not affected by the presence of the inactivation gate.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1

    Narahashi, T. Physiol. Rev. 54, 813–889 (1974).

  2. 2

    Hille, B. J. gen. Physiol. 69, 475–496 (1977).

  3. 3

    Woodhull, A. M. J. gen. Physiol. 61, 687–708 (1973).

  4. 4

    Schauf, C. F. & Davis, F. A. J. gen. Physiol. 67, 185–195 (1976).

  5. 5

    Campbell, D. T. & Hille, B. J. gen. Physiol. 67, 309–323 (1976).

  6. 6

    Ohmori, H. & Yoshii, M. J. Physiol., Lond. 267, 429–463 (1977).

  7. 7

    Nonner, W., Spalding, B. C. & Hille, B. Nature 284, 360–363 (1980).

  8. 8

    Yeh, J. Z. J. gen. Physiol. 73, 1–21 (1979).

  9. 9

    Wanke, E., Carbone, E. & Testa, P. L. Biophys. J. 26, 319–324 (1979).

  10. 10

    Carbone, E., Testa, P. L. & Wanke, E. Biophys. J. (submitted).

  11. 11

    Armstrong, C. M., Bezanilla, F. & Rojas, E. J. gen. Physiol. 62, 375–391 (1973).

  12. 12

    Hille, B. J. gen. Physiol. 66, 535–560 (1975).

  13. 13

    Carbone, E., Fioravanti, R., Prestipino, G. & Wanke, E. J. Membrane Biol. 43, 295–315 (1978).

  14. 14

    Bicher, H. I. & Ohki, S. Biochim. biophys. Acta 255, 900–904 (1972).

  15. 15

    Yeh, J. Z. & Narahashi, T. J. gen. Physiol. 69, 293–323 (1977).

  16. 16

    Rojas, E. & Rudy, B. J. Physiol., Lond. 262, 501–531 (1976).

Download references

Author information

Rights and permissions

To obtain permission to re-use content from this article visit RightsLink.

About this article

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.