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Evidence for Ca²⁺- and ATP-sensitive peripheral channels in nuclear pore complexes

Department of Physiology, University of Münster, Germany

¹Correspondence: Department of Physiology, University of Münster, Robert-Koch Str. 27a, D-48149 Münster, Germany. E-mail: oberlei{at}uni-muenster.de

In eukaryotic cells the nuclear envelope (NE) serves as a functional barrier between cytosol and nucleoplasm perforated by nuclear pore complexes (NPCs). Both active and passive transport of ions and macromolecules are thought to be mediated by the centrally located large NPC channel. However, 3-dimensional imaging of NPCs based on electron microscopy indicates the existence of additional small channels of unknown function located in the NPC periphery. By means of the recently developed nuclear hourglass technique that measures NE electrical conductance, we evaluated passive electrically driven transport through NPCs. In isolated Xenopus laevis oocyte nuclei, we varied ambient Ca²⁺ and ATP in the cytosolic solution and/or chelated Ca²⁺ in the perinuclear stores in order to assess the role of Ca²⁺ in regulating passive ion transport. We noticed that NE electrical conductance is large under conditions where macromolecule permeability is known to be low. In addition, atomic force microscopy applied to native NPCs detects multiple small pores in the NPC periphery consistent with channel openings. Peripheral pores were detectable only in the presence of ATP. We conclude that NPC transport of ions and macromolecules occurs through different routes. We present a model in which NE ion flux does not occur through the central NPC channel but rather through Ca²⁺- and ATP-activated peripheral channels of individual NPCs.—Shahin, V., Danker, T., Enss, K., Ossig, R., Oberleithner, H. Evidence for Ca²⁺- and ATP-sensitive peripheral channels in nuclear pore complexes.

Key Words: nuclear hourglass technique • Ca²⁺ stores • nuclear envelope • atomic force microscopy

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