Functional evidence of a role for two‐pore domain potassium channels in rat mesenteric and pulmonary arteries

Changing pH_o from 7.4 to 6.4 or 8.4 produced a depolarisation or hyperpolarisation, respectively, in mesenteric and pulmonary arteries. Anandamide (10 μM) or bupivacaine (100 μM) reversed the hyperpolarisation associated with alkaline pH_o, shifting the E_M of both vessels to levels comparable to that at pH 6.4. In pulmonary arteries, clofilium (100 μM) caused a significant reversal of hyperpolarisation seen at pH 8.4 but was without effect at pH 7.4.

K⁺ channel blockade by 4‐aminopyridine (4‐AP) (5 mM), tetraethylammonium (TEA) (10 mM), Ba²⁺ (30 μM) and glibenclamide (10 μM) depolarised the pulmonary artery. However, shifts in E_M with changes in pH_o remained and were sensitive to anandamide (10 μM), bupivacaine (100 μM) or Zn²⁺ (200 μM).

Anandamide (0.3–60 μM) or bupivacaine (0.3–300 μM) caused a concentration‐dependent increase in basal tone in pulmonary arteries.

RT–PCR demonstrated the expression of TASK‐1, TASK‐2, THIK‐1, TRAAK, TREK‐1, TWIK‐1 and TWIK‐2 in mesenteric arteries and TASK‐1, TASK‐2, THIK‐1, TREK‐2 and TWIK‐2 in pulmonary arteries. TASK‐1, TASK‐2, TREK‐1 and TWIK‐2 protein was demonstrated in both arteries by immunostaining.

These experiments provide evidence for the presence of two‐pore domain K⁺ channels in rat mesenteric and pulmonary arteries. Collectively, they strongly suggest that modulation of TASK‐1 channels is most likely to have mediated the pH‐induced changes in membrane potential observed in these vessels, and that blockade of these channels by anandamide or bupivacaine generates a small increase in pulmonary artery tone.