Electrical dimension of the nuclear envelope

Eukaryotic chromosomes are confined to the nucleus, which is separated from the rest of the cell by two concentric membranes known as the nuclear enve lope (NE). The NE is punctuated by holes known as nuclear pore complexes (N PCs), which provide the main pathway for transport of cellular material acr oss the nuclear-cytoplasmic boundary. The single NPC is a complicated octam eric structure containing more than 100 proteins called nucleoporins. NPCs function as transport machineries for inorganic ions and macromolecules. Th e most prominent feature of an individual NPC is a large central channel, s imilar to7 nm in width and 50 nm in length. NPCs exhibit high morphological and functional plasticity, adjusting shape to function. Macromolecules ran ging from 1 to >100 kDa travel through the central channel into (and out of ) the nucleoplasm. Inorganic ions have additional pathways for communicatio n between cytosol and nucleus. NE can turn from a simple sieve that separat es two compartments by a given pore size to a smart barrier that adjusts it s permeability to the metabolic demands of the cell. Early microelectrode w ork characterizes the NE as a membrane barrier of highly variable permeabil ity, indicating that NPCs are under regulatory control. Electrical voltage across the NE is explained as the result of electrical charge separation du e to selective barrier permeability and unequal distribution of charged mac romolecules across the NE. Patch-clamp work discovers NE ion channel activi ty associated with NPC function. From comparison of early microelectrode wo rk with patch-clamp data and late results obtained by the nuclear hourglass technique, it is concluded that NPCs are well-controlled supramolecular st ructures that mediate transport of macromolecules and small ions by separat e physical pathways, the large central channel and the small peripheral cha nnels, respectively. Electrical properties of the two pathways are still un clear but could have great impact on the understanding of signal transfer a cross NE and gene expression.