The ionic basis of the nerve impulse was well established over four decades ago by Hodgkin & Huxley (1952); and its application to myelinated nerve soon followed (Frankenhaeuser & Huxley, 1964). Huxley & Stämpfli (1949) had already provided clear evidence that conduction in peripheral myelinated nerve fibres was saltatory; and Rushton (1951) in a seminal theoretical analysis had made general predictions about the properties of myelinated fibres, particularly how these change as the fibre diameter changes. These predictions correspond extremely well with the situation that prevails in real axons.

One question remained unanswered, namely the nature of the axolemma under the myelin. Was the internodal axolemma similar to the nodal axolemma, i.e. capable of conducting but not doing so because of the insulating myelin sheath; or were the internodal electrophysiological properties quite different? The earliest study on conduction in single demyelinated fibres (Rasminsky & Sears, 1972) failed to resolve the question of whether demyelinated axons can conduct impulses in a continuous (as opposed to saltatory) manner. However, with improvements in technique, Bostock & Sears (1978) showed clearly that single undissected myelinated fibres in perfused ventral roots of normal rats treated with diptheria toxin to produce demyelination could indeed conduct impulses – but in a continuous manner, at less than one-twentieth of the velocity expected for normal stretches of the same fibre. This provided unequivocal evidence for the presence of Na+ channels in the now demyelinated internodal axon.