Referenced in: none

Automatically associated channels: ClC4

Title: Mimicry of a host anion channel by a Helicobacter pylori pore-forming toxin.

Authors: Daniel M Czajkowsky, Hideki Iwamoto, Gabor Szabo, Timothy L Cover, Zhifeng Shao

Journal, date & volume: Biophys. J., 2005 Nov , 89, 3093-101

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/16100263

Abstract
Bacterial pore-forming toxins have traditionally been thought to function either by causing an essentially unrestricted flux of ions and molecules across a membrane or by effecting the transmembrane transport of an enzymatically active bacterial peptide. However, the Helicobacter pylori pore-forming toxin, VacA, does not appear to function by either of these mechanisms, even though at least some of its effects in cells are dependent on its pore-forming ability. Here we show that the VacA channel exhibits two of the most characteristic electrophysiological properties of a specific family of cellular channels, the ClC channels: an open probability dependent on the molar ratio of permeable ions and single channel events resolvable as two independent, voltage-dependent transitions. The sharing of such peculiar properties by VacA and host ClC channels, together with their similar magnitudes of conductance, ion selectivities, and localization within eukaryotic cells, suggests a novel mechanism of toxin action in which the VacA pore largely mimics the electrophysiological behavior of a host channel, differing only in the membrane potential at which it closes. As a result, VacA can perturb, but not necessarily abolish, the homeostatic ionic imbalance across a membrane and so change cellular physiology without necessarily jeopardizing vitality.