The node of Ranvier in myelinated fibers is known to have an affinity to bind
cations.
Demyelination and remyelination due to abnormal expression of a
myelin protein may affect
cation binding or vice versa under pathological conditions. To study the
cation binding at the node of Ranvier in inherited demyelinating neuropathies associated with over- and under-expression of the peripheral
myelin protein 22 (PMP-22), the reaction with ferric ion and
ferrocyanide was used to visualize the
cation binding sites in biopsied nerves of four patients with
Charcot-Marie-Tooth disease type 1A (CMT1A) and two patients with
hereditary neuropathy with liability to pressure palsies (HNPP), and the results were compared with those of four patients having acquired neuropathies with normal PMP-22 expression. In CMT1A, nodal widening or paranodal
demyelination was associated with dense precipitates focally on both sides of the widened node. Although fainter precipitates were present at the node between remyelinated internodes, the percentage of nodes exhibiting the reaction product between normal and remyelinated internodes was not statistically different from that between normal internodes in CMT1A. In acquired neuropathies, on the other hand, the difference was significant between the two (P < 0.05), with reduction between normal and remyelinated internodes. At the nodes neighboring demylinated internodes, the percentage of nodes exhibiting the reaction product was reduced significantly in both CMT1A and acquired neuropathies, but to a lesser degree in CMT1A. Precipitates were clearly seen at the nodes neighboring a tomaculum in HNPP. The results suggest that preserved
cation binding at the node may allow nerves to keep the electrical excitability in CMT1A and HNPP where myelin remodeling takes place at high frequency.