Boyle 2015 Abstract MiP2015

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Kv1.3 channels in mitochondria: Are they important in cellular proliferation?

Link:

Boyle JP, Al-Owais MM, Peers C, Garrod F (2015)

Event: MiP2015

Kv1.3 is a member of the delayed rectifier family of voltage-activated potassium channels and has become a major therapeutic target because of its role in autoimmune diseases, in leukaemia, atherosclerosis and obesity and type 2 diabetes. Kv1.3 is not only expressed on the plasma membrane but also on the inner mitochondrial membrane [1] suggesting that some of its actions might be via modulation of mitochondrial function.

This was investigated in HEK293/Kv1.3 cells and human saphenous vein smooth muscle cells (HSVSMCs), using proliferation assays, immunocytochemistry and high resolution respirometry.

HEK293/Kv1.3 cells had significantly increased rates of proliferation compared to WT HEK293 cells. PAP-1, a selective, cell permeant Kv1.3 inhibitor, reduced proliferation in both HEK293/Kv1.3 and HSVSMCs. Channel expression in both the plasma membrane and mitochondria was confirmed using mitotracker in conjunction with immunocytochemical detection of Kv1.3. Mitochondrial expression of the channel was confirmed in both cell types. In addition, the functional expression of the Kv1.3 channel in the plasma membrane was confirmed using patch clamp electrophysiology. High resolution respirometry demonstrated that HEK293/Kv1.3 cells were significantly more metabolically active than WT HEK cells with both increased OXPHOS and glycolytic activity.

Thus mitochondrial Kv1.3 may contribute to increased mitochondrial respiration. This will be further investigated using additional permeant and impermeant inhibitors of the Kv1.3 channel.


O2k-Network Lab: UK Leeds Peers C


Labels: MiParea: Respiration, mt-Membrane 


Organism: Human  Tissue;cell: Endothelial;epithelial;mesothelial cell, HEK 


Coupling state: OXPHOS 

HRR: Oxygraph-2k  Event: D1, Oral  MiP2015 

Affiliations

Cardiovascular & Diabetes Research, LICAMM, Univ Leeds, UK. - j.p.boyle@leeds.ac.uk

References

  1. Szabo I, Bock J, Jekle A, Soddeman M, Adams C, Lang F, Zoratti M, Gulbins E (2005) A novel potassium channel in lymphocyte mitochondria. J Biol Chem 280 12790-8.