Action Potentials and Membrane Currents in the Human Node of Ranvier

Action potentials and membrane currents were recorded in single human myelinated nerve fibres under current- and voltage-clamp conditions at room temperature. Nerve material was obtained from patients undergoing nerve graft operations. Successful recordings were made in 11 nerve fibres. In Ringer's solution, large transient Na currents were recorded, which could be blocked completely with tetrodotoxin. Partial block of these currents with 3 nM tetrodotoxin was used to reduce the voltage-clamp error due to series resistance. Outward K currents were very small in intact nerve fibres, but had a large amplitude in fibres showing signs of paranodal demyelination. In isotonic KCl, the K current could be separated into three components: two fast components (Kf1 and Kf2) and one slow component (Ks). Time constants and steady-state activation and inactivation of Na permeability and of fast and slow K conductance were measured within the potential range of -145 mV to +115 mV. From these parameters, the corresponding rate constants were calculated and a mathematical model based on the Frankenhaeuser-Huxley equations was derived. Calculated action potentials closely matched those recorded. Single calculated action potentials were little affected by removing the fast or slow K conductance, but the slow K conductance was required to limit the repetitive response of the model to prolonged stimulating currents.