Non technical summary Contraction of the muscle in the walls of blood vessels is controlled by the movement of ions into or out of the muscle cells, through proteins called ion channels. By allowing potassium (K + ) to leave the cell, K + -selective ion channels keep arteries dilated. In the pulmonary artery, which carries blood to the lung for gas exchange, a type of K + channel called TASK-1 is thought to play an important role in this regulation, but we observed that the pulmonary arteries from mice that lack the TASK-1 protein do not display any altered properties compared to wild-type (normal) mice. We found, however, that the pattern of K + flux in muscle cells from mouse pulmonary artery is different from that of other species, including human. Our results question the use of mouse as a model for human pulmonary artery.Abstract The acid-sensitive, two-pore domain K + channel, TASK-1, contributes to the background K + conductance and membrane potential (E m ) of rat and human pulmonary artery smooth muscle cells (PASMCs), but its role in regulating tone remains elusive. This study aimed to clarify the role of TASK-1 by determining the functional properties of pulmonary artery (PA) from mice in which the TASK-1 gene was deleted (TASK-1/3 KO), in comparison with wild-type (WT) C57BL/6 controls. Small vessel wire myography was used to measure isometric tension developed by intact PA. E m and currents were recorded from freshly isolated PASMCs using the perforated patch-clamp technique. Reverse transcription-polymerase chain reaction (RT-PCR) was used to estimate K + channel expression. We could find no difference between PA from WT and TASK-1/3 KO mice. They showed similar constrictor responses to a range of agonists and K + concentrations, the K + channel blockers 4-aminopyridine, tetraethylammonium ions and XE991. Treprostinil, proposed to dilate by activating TASK-1, was just as effective in TASK-1/3 KO arteries. Blocking Ca 2+ influx with nifedipine (1 μM) or levcromakalim (10 μM) had no effect on resting tone in either strain. The resting E m of PASMCs and its responses to K + channel blockers were unchanged in TASK-1/3 KO mice as were voltage-activated K + currents, including the non-inactivating K + current (I KN ) measured at 0 mV. The E m was, however, depolarised in comparison with other species. Mouse I KN was much smaller than in rat and showed no sensitivity to pH. The results imply that TASK-1 does not form a functional channel in mouse PASMCs. Abbreviations LV, left ventricle; PA, pulmonary artery; PASMC, pulmonary artery smooth muscle cell; RV, right ventricle; S, intra-ventricular septum; SMC, smooth muscle cell.

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