Introduction (by R. Rüdel)

After Hodgkin and Huxley (1952a,b) had described the currents underlying excitation of the squid axon, many investigators attempted to explore the mechanism of excitation in other cells such as myelinated nerve (Frankenhäuser & Huxley, 1964) and mammalian heart (Noble, 1966). I joined Trautwein's laboratory in 1965, where at the time experiments were carried out with the aim “to clamp the sodium current” in sheep Purkinje fibres (Dudel et al., 1966, Dudel & Rüdel, 1970). During a postdoctoral fellowship in Andrew Huxley's laboratory in 1968-70, I was diverted to the inward spread of activation in skeletal muscle in accordance with Huxley's more recent interests, but, back in Germany, I returned to excitation, this time to disorders of excitation in human muscle, in particular in the myotonias (Rüdel & Lehmann-Horn, 1985) and periodic paralyses (Rüdel & Ricker, 1958)

Inactivation mechanisms

In their first mathematical description of the transient sodium current, lNa(t), through the membrane of excitable cells, Hodgkin and Huxley (1952d; HH) postulated two independent mechanisms for the activation, m, and inactivation, h, of the passage of ions through membranes. The equation lNa(t) = gNa (E –ENa) m3h, with gNa the maximum sodium conductance, and (E - –Na) the difference between the membrane potential and the sodium equilibrium potential, gave good fits to the experimental data, when first-order kinetics were assumed to be valid for the time dependence of m and h. In modern terms, the sodium ions are assumed to pass the membrane through channel proteins which are able to adopt conducting and nonconducting states.