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 undergoin
g nerve graft operations. Successful recordings were made in 11 nerve
fibres. In Ringer's solution, large transient Na currents were recorde
d, which could be blocked completely with tetrodotoxin. Partial block
of these currents with 3 nM tetrodotoxin was used to reduce the voltag
e-clamp error due to series resistance. Outward K currents were very s
mall in intact nerve fibres, but had a large amplitude in fibres showi
ng signs of paranodal demyelination. In isotonic KCl, the K current co
uld be separated into three components: two fast components (K-f1 and
K-f2) and one slow component (K-s). Time constants and steady-state ac
tivation and inactivation of Na permeability and of fast and slow K co
nductance were measured within the potential range of -145 mV to +115
mV. From these parameters, the corresponding rate constants were calcu
lated and a mathematical model based on the Frankenhaeuser-Huxley equa
tions 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 wa
s required to limit the repetitive response of the model to prolonged
stimulating currents.