Characterization ofClostridial botulinum neurotoxin channels in neuroblastoma cells
- 75 Downloads
The channel and chaperone activities ofClostridial botulinum neurotoxin (BoNT) A were investigated in Neuro 2a neuroblastoma cells under conditions that closely emulate those prevalent at the endosome. Channel activity occurs in bursts interspersed between periods of little or no activity. The channels are voltage dependent, opening only at negative voltages. Within bursts, the channel resides preferentially in the open state. The channels open to a main conductance of 105 ± 5 pS or 65 ± 4 pS in 200 mM CsCl or NaCl, respectively. The BoNT channels display a conspicuous subconductance of 10 ± 2 pS. The neuroblastoma cell line appears, therefore, to be a suitable system to characterize the BoNT channel and to pursue evaluation of plausible strategies for targeted drug delivery thereby minimizing the requirement forin vivo animal testing.
KeywordsBotulinum neurotoxin Channels Chaperones Targeted drug screen Protein translocation
Unable to display preview. Download preview PDF.
- Hille B (2001)Ion Channels of Excitable Cells, 3rd Edition (Sinauer: Sunderland, MA).Google Scholar
- Hoch DH, M Romero-Mira, BE Ehrlich, A Finkelstein, BR DasGupta and LL Simpson (1985) Channels formed by botulinum, tetanus, and diphtheria toxins in planar lipid bilayers: relevance to translocation of proteins across membranes.Proc. Natl. Acad. Sci. USA 82, 1692–1696.PubMedCentralPubMedCrossRefGoogle Scholar
- Krantz BA, A Finkelstein and RJ Collier (2005a) Protein Translocation through the anthrax toxin transmembrane pore is driven by a proton gradient.J. Mol. Biol. 2005 Dec 1; [Epub ahead of print].Google Scholar