The two-pore domain potassium channel (K2P) family is important in determining neuronal excitability. Of these K2P channels, the TASK subfamily are thought to be particularly significant in a number of neuronal types. K2P channels are modulated by a variety of physico-chemical and pharmacological factors. We have investigated the differential modulation of TASK channels by external copper.

Recordings were made using the whole-cell patch clamp technique on tsA-201 cells transiently transfected with hTASK-1, hTASK-2 and hTASK-3. TASK-3 currents were potently blocked by copper, with 10 mM producing an inhibition of 75 ± 3% (n = 8, see also Gruss et al 2004, Mol Pharmacol, 66, 530–537). Copper was less effective at blocking TASK-1 channels (41 ± 3%, n = 8 at 10 mM) whilst TASK-2 channels were unaffected by copper (2 ± 2%, n = 8 at 100 mM). TASK-3 channel block by copper could be occluded (14 ± 5%, n = 8 at 10 mM) by pre-treatment with the sulfhydryl-group reducing agent dithiothreitol (DTT, 5mM), suggesting copper acts on external cysteine residues. To eliminate the possibility of the ion indirectly acting on the channel following the generation of reactive oxygen species, copper was tested in the presence of 10mM mannitol. No change in the extent of block was found (79 ± 7%, n = 5 at 10 mM).

These data suggest that copper blocks TASK-3 channels by binding to cysteine residues and altering the redox state of their sulfhydryl groups.