Nuclear pore complex ion channels (Review)

Abstract

It is currently thought that nuclear pore complexes (NPCs) primarily govern nucleocytoplasmic interactions via selective recognition and active transport of macromolecules. However, in various nuclear preparations, patch-clamp and fluorescence, luminiscence and ion microscopy support classical microelectrode measurements indicating that monoatomic ion flow across the nuclear envelope (NE) is strictly regulated. Gating of large conductance nuclear envelope ion channels (NICs) somewhat resembles that of gap junctional channels. In other respects, NICs are distinct in that they require cytosolic factors, are blocked by wheat germ agglutinin and are blocked and/or modified by antibodies to epitopes of NPC glycoproteins. Therefore, NIC activity, recorded as electrical current/conductance is likely to be intrinsic to NPCs. This observation suggests a potential use for the patch-clamp technique in establishing the mechanisms underlying nuclear pore gating in response to cytosolic and nucleosolic factors such as transcription and growth factors, oncogene and proto-oncogene products and receptors for retinoids, steroids and thyroid hormone. NIC activity may also be useful in evaluating the mechanisms of nuclear import of foreign nucleic acid material such as that contained in virons and viroids. Finally, in consideration to the electrophysiological data accumulated so far, the study of nuclear pore ion channel activity may help our understanding of other important issues such as cell suicide, programmed cell death or apoptosis.