Background: 

Potassium channels have been proposed to play a key role in the progression of organ fibrosis. Recently, it has been shown that the Calcium-activated potassium channel K_Ca3.1 control crucial fibroblast functions like proliferation and migration.

Aims: 

i) Characterization of potassium channels involved in murine renal fibroblasts. ii) To study the regulation of the activity of these newly characterized potassium channels by different growth factors that are important in the pathophysiology of renal fibrosis.

Method: 

Characterization of K2P channels by whole-cell and cell-attached patch clamp experiments. Verification of the channels with the real-time PCR and with immunfluoresence experiments. Investigation of migration and proliferation with the bifocal microscopy.

Results: 

In murine renal fibroblasts we detected the expression of different members of two-pore-domain potassium channels (K₂P) family. Among a total of fifteen members in this potassium family, the renal fibroblast were found to be expressing six. In the quantitative RT-PCR experiments, TREK-1, TREK-2 and THIK-1 were the most dominant K2P. In whole cell and cell-attached experiments, we tested specific activators or inhibitors like changes in pH and temperature, mechanical stress, volatile anaesthetics, unsaturated fatty acids, antiarrhythmic and antidepressive agents. We have the evidence, that THIK-1 has a major contribution in the arachidonic-acid sensitive current. Mitogenic stimulation of fibroblast with profibrotic agents b-FGF and TGF-b led to 70 percent downregulation of channel activity in renal fibroblasts.

Conclusion: 

Aside from previously described Ca-activated potassium channels renal fibroblasts also possess a distinct array of K2P-potassium channels. The show typical stimulation behaviour and are regulated in the presence of profibrotic stimuli. In the clinical context these channels might represent new pharmacological target against renal fibrosis.

Figure 1