APPS November 2002 Meeting Abstract 2416


Joy H.C. Tan, Weihong Liu, David A. Saint, Department of Physiology, University of Adelaide, SA 5005.

Stretch-activated ion channels have been reported in many cell types eg., cardiac1, 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 (Po) of the channel increased with increasing amounts of suction applied (Po ≈ 0.005 with no pressure; ≈ 0.328 with 90 cm.H2O: membrane holding potential (Vm) = 40 mV, pHi = 7.2, n = 5). Lowering the intracellular pH also increased channel activity (Po = 0.005 at pH 7.2; Po = 0.16 at pH 5.5: no suction, Vm held at 40 mV). Po 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, Po was 0.048 0.023. Po increased to 0.348 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.

(1) Kawakubo T, Naruse K, Matsubara T, Hotta N, Sokabe M. American Journal of Physiology. 1999;276:H1827-1838.

(2) Kim DJ. General Physiology. 1992;100:1021-1040.

(3) Maingret F, Patel AJ, Lesage F, Lazdunski M, Honore EJ. Biological Chemistry. 1999;274:26691-26696.

(4) Farrugia G, Holm AN, Rich A, Sarr MG, Szurszewski JH, Rae JL. Gastroenterology. 1999;117(4):900-905.

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