Characterization of Clostridial botulinum neurotoxin channels in neuroblastoma cells.
The channel and chaperone activities of Clostridial 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 for in vivo animal testing.
Fisher
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A
Section of Neurobiology, Division of Biological Sciences, University of California San Diego, La Jolla, 92093-0366, USA.
Montal
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M
D000818:Animals; D019274:Botulinum Toxins, Type A / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D004594:Electrophysiology; D011992:Endosomes / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism; D051379:Mice; D018832:Molecular Chaperones / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D021381:Protein Transport
D007473:Ion Channels; D018832:Molecular Chaperones; D019274:Botulinum Toxins, Type A