Reduced expression of voltage-gated sodium channels in neurons cultured from trisomy 16 mouse hippocampus.

Voltage-gated sodium channels are responsible for the initial depolarizing phase of the action potential. In hippocampal neurons cultured from trisomy 16 (Ts16) mice (a model for Down's syndrome), the maximum inward conductance mediated by these channels was reduced 47% relative to control diploid neurons. This reduced conductance was reflected in a 35% decrease in binding of radiolabeled saxitoxin, a sodium channel-specific ligand, indicating expression of fewer channels in these neurons. The mRNAs encoding the alpha and beta 1 subunits were, however, present at the same levels in Ts16 neurons and control diploid neurons. Thus, the altered regulation of voltage-gated sodium channels in Ts16 neurons is apparently a post-transcriptional event and possible mechanisms are discussed.