An investigation of the occurrence and properties of the mitochondrial intermediate-conductance Ca2+-activated K+ channel mtKCa3.1.
The mitochondrial intermediate-conductance Ca2+-activated K+ channel mtKCa3.1 has recently been discovered in the HCT116 colon tumor-derived cell line, which expresses relatively high levels of this protein also in the plasma membrane. Electrophysiological recordings revealed that the channel can exhibit different conductance states and kinetic modes, which we tentatively ascribe to post-translational modifications. To verify whether the localization of this channel in mitochondria might be a peculiarity of these cells or a more widespread feature we have checked for the presence of mtKCa3.1 in a few other cell lines using biochemical and electrophysiological approaches. It turned out to be present at least in some of the cells investigated. Functional assays explored the possibility that mtKCa3.1 might be involved in cell proliferation or play a role similar to that of the Shaker-type KV1.3 channel in lymphocytes, which interacts with outer mitochondrial membrane-inserted Bax thereby promoting apoptosis (Szabò, I. et al., Proc. Natl. Acad Sci. USA 105 (2008) 14861-14866). A specific KCa3.1 inhibitor however did not have any detectable effect on cell proliferation or death.
Sassi
Nicola
N
Department of Experimental Biomedical Sciences, University of Padova, Italy.
De Marchi
Umberto
U
Fioretti
Bernard
B
Biasutto
Lucia
L
Gulbins
Erich
E
Franciolini
Fabio
F
Szabò
Ildikò
I
Zoratti
Mario
M
D017209:Apoptosis / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D045325:HCT116 Cells; D006801:Humans; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494826:BAX protein, human; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496923:KCNN4 protein, human; D033681:Mitochondrial Membrane Transport Proteins; D051028:bcl-2-Associated X Protein