Ion channels in human axons

Although human myelinated axons appear to generate and conduct impulses in the same way as those of other species, they are more prone to ectopic activity than rat axons and show other electrophysiological differences which suggest they may have different populations of ion channels. This study was designed to investigate this question, and this thesis describes the first direct recordings of ion channel currents in human peripheral myelinated axons, using patch clamping and macroscopic voltage clamping. Patch-clamp recordings from nodes of Ranvier, paranodes and internodes of human axons revealed voltage-dependent, tetrodotoxin-sensitive sodium channels, and at least three types of depolarisation-activated potassium channel. Conventional nodal voltage-clamp techniques showed a tetrodotoxin-sensitive sodium current, a small, fast potassium current (consisting of two components), and a slow potassium current. The voltage dependence, kinetics and conductances of these channels are described, together with the characteristics of the macroscopic currents. Measurements from isolated patches and intact axons are compared and found to be in close agreement; similarly, ion channels and currents in human axons appear indistinguishable from those in rat and amphibian axons. A simple Hodgkin-Huxley type model was fitted to the nodal voltage-clamp recordings, and was able to simulate action potentials and repetitive activity. The model predicted functions for the ionic currents which are the same as in other mammals. It is clear that the major voltage-dependent ion channels in human axons are closely similar to those in other species; some other explanation, such as differences in the distribution of the channels, is needed to explain the differences between human and rat axons which have been observed in vivo.