Density of sodium channels in mammalian myelinated nerve fibers and nature of the axonal membrane under the myelin sheath.

Abstract

The density of Na+ channels in mammalian myelinated fibers was estimated from measurements of the binding of [3H]saxitoxin to rabbit sciatic nerve. Binding both to intact and to homogenized nerve consisted of a linear, nonspecific, component and a saturable component that represents binding to the Na+ channel. The maximum saturable binding capacity in intact nerve was 19.9 .+-. 1.9 f[femto]mol .cntdot. mg wet-1; the equilibrium dissociation constant, Kt, was 3.4 .+-. 2.0 nM. Homogenization made little difference, the maximum binding capacity being 19.9 .+-. 1.5 fmol .cntdot. mg wet-1 with Kt = 1.3 .+-. 0.7 nM. These values correspond to a density of about 700,000 Na+ channels per node, i.e., about 12,000 per .mu.m2 of nodal membrane. From the difference between the values of maximum saturable binding capacity in intact and homogenized preparation, given the statistical uncertainty of their estimate, it seems that the internodal membrane can have no more than about 25 channels/.mu.m2. The significance of these findings for saltatory conduction and in demyelinating disease was discussed.