Role of Kv1.3 mitochondrial potassium channel in apoptotic signalling in lymphocytes.
Mitochondria have been shown to play a pivotal role in apoptotic signalling in various cell types. We have recently reported that in lymphocytes the voltage-gated potassium channel Kv1.3, known to reside in the plasma membrane, is active also in the inner mitochondrial membrane. Upon induction of apoptosis, outer-membrane inserted Bax binds to and inhibits Kv1.3 resulting in hyperpolarization, an increase in reactive oxygen species production and cytochrome c release. In cells lacking Kv1.3 these events do not take place. Here, we present new data which further corroborates an important role of this channel in the sequence of events leading to Bax-induced cytochrome c release. Recombinant Kv1.3, when pre-incubated with Bax, prevents the actions of Bax at the level of mitochondria. Furthermore, we report the presence of Kv1.3 protein in mitochondria from PC3 and MCF-7 cancer cells, suggesting that this channel might play a role in the apoptotic signalling not only in lymphocytes but also in other cells.
Gulbins
Erich
E
Department of Molecular Biology, University of Essen, Hufelandstrasse 5., Essen, Germany. erich.gulbins@uni-due.de
Sassi
Nicola
N
Grassmè
Heike
H
Zoratti
Mario
M
Szabò
Ildikò
I
D017209:Apoptosis / Q000502:physiology*; D001667:Binding, Competitive; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D051664:Kv1.3 Potassium Channel / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012604:Scorpion Venoms / Q000378:metabolism; D015398:Signal Transduction; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494826:BAX protein, human; D051664:Kv1.3 Potassium Channel; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D012604:Scorpion Venoms; D051028:bcl-2-Associated X Protein; C077910:margatoxin; D045304:Cytochromes c