NA+-ACTIVATED K+ CHANNELS LOCALIZED IN THE NODAL REGION OF MYELINATED AXONE OF XENOPUS

1. A potassium channel activated by internal Na+ ions (K-Na(+) channel) was identified in peripheral myelinated axons of Xenopus laevis using the cell-attached and excised configurations of the patch clamp technique. 2. The single-channel conductance for the main open state was 88 pS with [K+](o) = 105 mM and 34 pS with [K+](o) = 2.5 mM ([K+](i) = 105 mM). The channel was selectively permeable to K+ over Na+ = ions. A characteristic feature of the K-Na(+) channel was the frequent occurrence of subconductance states. 3. The open probability of the channel was strongly dependent on the concentration of Na+ ions at the inner side of the membrane. The half-maximal activating Na+ concentration and the Hill coefficient were 33 mM and 2.9, respectively. The open probability of the channel showed only weak potential dependence. 4. The K-Na(+) channel was relatively insensitive to external tetraethylammonium (TEA(+)) in comparison with voltage-dependent axonal K+ channels; the half-maximal inhibitory concentration (IC50) was 21.3 mM (at -90 mV). In contrast, the channel was blocked by low concentrations of external. Ba2+ and Cs+ ions, with IC50 values of 0.7 and 1.1 mM, respectively (at -90 mV). The block by Ba2+ and Cs+ was more pronounced at negative than at positive membrane potentials. 5. A comparison of the number of K-Na(+) channels in nodal and paranodal patches from the same axon revealed that the channel density was about 10-fold higher at the node of Ranvier than at the paranode. Moreover, a correlation between the number of K-Na(+) channels and voltage-dependent Na+ channels in the same patches was found, suggesting co-localization of both channel types. 6. As weakly potential-dependent ('leakage') channels, axonal K-Na(+) channels may be involved in setting the resting potential of vertebrate axons. Simulations of Na+ ion diffusion suggest two possible mechanisms of activation of K-Na(+) channels: the local increase of Na+ concentration in a cluster of Na+ channels during a single action potential or the accumulation in the intracellular axonal compartment during a train of action potentials.