APPS November 2002 Meeting Abstract 2416

Stretch-activated ion channels have been reported in many cell types eg., cardiac^{1, 2, 3} and intestinal smooth muscle cells⁴. They are thought to be important for transducing mechanical stretch into electrical signals. Patch-clamp techniques were used in this study to characterise a large stretch-sensitive channel found in rat ventricular myocytes. In cell-attached and ripped-off patches, suction applied to the pipette activated a potassium-selective ion channel. Open probability (P_o) of the channel increased with increasing amounts of suction applied (P_o ≈ 0.005 with no pressure; ≈ 0.328 with 90 cm.H₂O: membrane holding potential (Vm) = 40 mV, pH_i = 7.2, n = 5). Lowering the intracellular pH also increased channel activity (P_o= 0.005 at pH 7.2; P_o = 0.16 at pH 5.5: no suction, Vm held at 40 mV). P_o was also increased by intracellular ATP at a more acidic intracellular pH. At a pH of 6 with no ATP at the intracellular membrane face, P_o was 0.048 ą 0.023. P_o increased to 0.348 ą 0.13 with 3 mM ATP (no suction applied). The channel was however not sensitive to ATP at a physiological intracellular pH of 7.2 These channels have characteristics of the TREK-1 channel, a member of the recently cloned two pore, four transmembrane domain family of potassium channels³. Using RT-PCR, TREK-1 was found to be expressed in the rat heart reinforcing the conclusion that the channels being investigated are TREK-1. However, so far, there are no reports of activation by intracellular ATP of TREK-1 channels. Cardiac potassium selective stretch-activated channels might have an important role in hyperpolarising the membrane potential in order to prevent excess Ca²⁺ influx which can be deleterious for the cell³. These channels might also be involved in shortening the action potential duration when the heart is stretched.