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A heteromeric potassium channel involved in the modulation of the plasma membrane potential is essential for the survival of African trypanosomes
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 3199326
Author(s) Steinmann, Michael E.; Gonzalez-Salgado, Amaia; Buetikofer, Peter; Maeser, Pascal; Sigel, Erwin
Author(s) at UniBasel Mäser, Pascal
Year 2015
Title A heteromeric potassium channel involved in the modulation of the plasma membrane potential is essential for the survival of African trypanosomes
Journal The FASEB journal
Volume 29
Number 8
Pages / Article-Number 3228-3237
Keywords Trypanosoma brucei, electrophysiology, Xenopus laevis oocytes
Abstract

Discovery of novel drug targets may lead to improved treatment of trypanosomiasis. We characterize here 2 gene products of Trypanosoma brucei that are essential for the growth of bloodstream form (BSF) parasites, as shown by RNA interference (RNAi)-mediated down-regulation of the individual mRNAs. The primary sequences of the 2 proteins-protein encoded by gene Tb927.1.4450 (TbK1) and protein encoded by gene Tb927.9.4820 (TbK2)-indicate that both belong to the family of putative, Ca(2+)-activated potassium channels. The proteins were expressed in Xenopus laevis oocytes and their functions investigated by use of electrophysiological techniques. Only combined expression of TbK1 and TbK2 results in the formation of sizeable currents, indicating that these proteins probably assemble into a heteromeric ion channel. The current mediated by this channel shows little time and voltage dependence and displays a permeability ratio of K(+)/Na(+) of >20. The known potassium channel blocker barium inhibits this channel with a half-maximal inhibitory concentration (IC50) of 98 ± 15 μM. The membrane potential of trypanosomes was measured with a fluorescent dye. Individual RNAi-mediated down-regulation of TbK1 or TbK2 eliminates a potassium conductance in the plasma membrane of BSF. Thus, this heteromeric potassium channel is involved in the modulation of the plasma membrane potential and represents a novel drug target in T. brucei.-Steinmann, M. E., González-Salgado, A., Bütikofer, P., Mäser, P., Sigel, E. A heteromeric potassium channel involved in the modulation of the plasma membrane potential is essential for the survival of African trypanosomes.

Publisher FASEB]
ISSN/ISBN 0892-6638
edoc-URL http://edoc.unibas.ch/dok/A6420017
Full Text on edoc No
Digital Object Identifier DOI 10.1096/fj.15-271353
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/25868728
ISI-Number WOS:000358796900012
Document type (ISI) Article
 
   

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29/03/2024