Interactions of guanidinium ions with sodium channels in frog myelinated nerve fibre.

1. The effects of external guanidinium ions on fast and slow inactivating currents flowing through sodium channels of the frog myelinated nerve fibre (Benoit, Corbier & Dubois, 1985) were analysed under voltage-clamp conditions. 2. When external sodium ions were partially replaced by guanidinium ions, the fast inactivating current was preferentially reduced and was absent in a solution containing guanidinium ions as the only external permeant cations. The inactivation time constants of both fast and slow currents were not significantly modified by the replacement of sodium ions by guanidinium ions. 3. Substitution of guanidinium ions for all sodium ions shifted the steady-state inactivation curve of the slow inactivating current towards positive voltages. 4. The voltage dependence of the activation of fast and slow inactivating currents was shifted towards positive voltages by guanidinium ions. Moreover, the activation-voltage curve of the slow inactivating current, which was biphasic under control conditions, was monophasic when guanidinium ions were substituted for all sodium ions. 5. Whereas the slow inactivating current could be carried by guanidinium ions, these cations were not only impermeant through the sodium channels which give rise to the fast inactivating current but also blocked this type of channel with an apparent dissociation constant of 49 mM. 6. It is concluded that guanidinium appears to be an efficient tool for further separating the two types of inactivating current and studying the properties of the slow inactivating current. These results are consistent with the suggestion that there are two types of sodium channels, fast and slow, with guanidinium ions being permeant only through the slow ones.