In pulmonary artery (PA) smooth muscle cells (SMC), compelling evidence suggests that TWIK-related acid sensitive K⁺-1 (TASK-1) channels contribute to the background K⁺ current that supports the membrane potential (E_m). Due to poor selectivity of TASK-1 channel modulators, the role of the channel in the functional regulation of PA tone remains elusive. The purpose of this study was to determine the properties of PA from mice in which the TASK-1 and TASK-3 genes were deleted (TASK1/3 knockout, KO), in comparison with C57BL/6 wild type (WT) control mice. Intra-PAs were isolated from adult male WT and KO mice. Vessels were mounted on a wire myograph for isometric tension recording or processed for gene expression studies using reverse-transcription polymerase chain reaction (RT-PCR). Patch clamp experiments in the perforated-patch configuration were conducted on freshly isolated PASMC. RT-PCR confirmed TASK-1 expression in PA from WT but not KO mice, whereas TASK-3 was absent in both strains. The TASK-1/3 KO mice could therefore be used to study the role of TASK-1 in mouse PA. If TASK-1 is a key determinant of E_m, deletion of the TASK-1 gene might be expected to cause depolarisation, thereby stimulating Ca²⁺ influx and intrinsic tone. The addition of 10mM KCl, the K⁺ channel modulators 4-aminopyridine (4-AP, 1mM) and levcromakalim (10µM), or the L-type calcium channel blocker nifedipine (1µM) had no significant effect on the tone of PAs from either KO (N=3) or WT mice (N=3). These results imply that E_m is not depolarised and that PAs are fully dilated in both groups. The contractile responses of PA to phenylephrine, serotonin and PGF2α were also similar between the two mouse strains. The non inactivating K⁺ current (I_K(N)), recorded after clamping the E_m at 0 mV for 5-6 minutes, was similar in PASMC from WT (0.2 ± 0.1 pA/pF, N=4) and KO (0.2 ± 0.1 pA/pF, N=3) mice. I_K(N) was unchanged in the presence of 10mM tetraethylammonium chloride (TEA) to block BK_Ca channels, but was much smaller than I_K(N) recorded from rat PASMC in the same conditions (1.7 ± 0.3 pA/pF, N=4). Unlike the rat counterpart, murine I_K(N) showed no sensitivity to pH changes between 6.3 and 8.4, in either WT or KO mice. No differences were detected in the mRNA levels of TASK-2, TASK-5, TWIK-2, K_v1.5 or K_v2.1 between WT (N=3) and KO (N=3) mice. PA isolated from KO mice failed to develop intrinsic tone and displayed unaltered vasoconstrictor responses. The absence of TASK-1 in PA SMC did not affect I_K(N) and was not compensated by up-regulation of other K⁺ channel subunits. The results question the importance of TASK-1 in mouse PA and highlight species differences in the resting K⁺ conductance.