title: Contractile and electrophysiological properties of pulmonary artery smooth muscle are not altered in TASK-1 knockout mice.
abstract: The acid-sensitive, two-pore domain K+ channel, TASK-1, contributes to the background K+ conductance and membrane potential (Em) 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. Em 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 Ca2+ influx with nifedipine (1 μM) or levcromakalim (10 μM) had no effect on resting tone in either strain. The resting Em 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 (IKN) measured at 0 mV. The Em was, however, depolarised in comparison with other species.Mouse IKN 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.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: Boris
authors.initials: B
authors.lastname: Manoury
authors.forename: Caroline
authors.initials: C
authors.lastname: Lamalle
authors.forename: Roberta
authors.initials: R
authors.lastname: Oliveira
authors.forename: Joy
authors.initials: J
authors.lastname: Reid
authors.forename: Alison M
authors.initials: AM
authors.lastname: Gurney
mesh_terms: D000818:Animals; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000235:genetics / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques / Q000379:methods; D024683:Potassium Channels, Tandem Pore Domain / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D011651:Pulmonary Artery / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000235:genetics / Q000502:physiology*
chemical_list: D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; C420132:potassium channel subfamily K member 3