Trek-like potassium channels in rat cardiac ventricular myocytes are activated by intracellular ATP

Large (111+/-3.0 pS) K+ channels were recorded in membrane patches from adult rat ventricular myocytes using patch-clamp techniques. The channels were not blacked by 4-AP (5 mm), intracellular TEA (5 mM) or glybenclamide (100 mm). Applying stretch to the membrane (as pipette suction) increased channel open probability (P,,) in both cell-attached and isolated patches (typically, P-o approximate to 0.005 with no pressure; approximate to0.328 with 90 cm H2O: V-m = 40 mV, pH(i) = 7.2). The channels were activated by a decrease in intracellular pH; decreasing pH(i) to 5.5 from 7.2 increased P-o to 0.16 from approx. 0.005 (no suction, V-m held at 40 mV). These properties are consistent with those demonstrated for TREK-1, a member of the recently cloned tandem pore family. We confirmed, using RT-PCR, that TREK-1 is expressed in rat ventricle, suggesting that the channel being recorded is indeed TREK-1. However, we show also that the channels are activated by millimolar concentrations of intracellular ATP. At a pH of 6 with no ATP at the intracellular membrane face, P-o was 0.048+/-0.023, whereas P-o increased to 0.22+/-0.1 with 1 mm ATP, and to 0.348+/-0.13 with 3 mM (n = 5; no membrane stretch applied). The rapid time course of the response and the fact that we see the effect in isolated patches appear to preclude phosphorylation. We conclude that intracellular ATP directly activates TREK-like channels, a property not previously described.