In the heart, mechanical forces on the myocardium can induce electrical disturbances (mechano-electric feedback or MEF). It seems likely that MEF involves stretch sensitive non specific cation channels (SACs) and mechanosensitive potassium channels in the myocardial cell membrane (Hu and Sachs, 1997; Kim, 1992).
Using patch clamp techniques we have characterised a mechanosensitive potassium channel in isolated rat ventricular myocytes. The channel is highly selective for K+, has a conductance of c.100 pS, and responds strongly to suction applied to the patch electrode. We propose that this channel is TREK-1, a member of the 4T2P gene family (Lesage and Lazdunski, 2000) since TREK-1, when expressed in heterologous systems, has been shown to have the combination of properties that matches our functional measurements in cardiac cells (Maingret et al, 1999), and RT-PCR has shown the gene for TREK-1 to be expressed in the heart (Aimond et al, 2000).
In order to control dispersion of repolarisation, the cardiac action potential has a very different morphology in different parts of the heart, a crucial determinant of this action potential heterogeneity being the variation in the expression level of the voltage dependent potassium channels. Here we report that the gene expression level of TREK-1 is also spatially heterogenenous in adult rat ventricle. Using real-time RT-PCR against GAPDH as a comparator gene, TREK-1 expression was found to be 0.34 ± 0.14 in endocardial cells compared to 0.02 ± 0.02 in epicardial cells (p < 0.05). In agreement with this differential gene expression, whole cell TREK-1 current density, activated by chloroform, was larger in endocardial cells (0.8 ± 0.27 pA/pF) compared to epicardial cells (0.21 ± 0.06 pA/pF) (p < 0.05).
We hypothesise that this differential expression of TREK-1 may be related to the distribution of stress across the ventricular wall and may play a role in synchronisation of repolarisation during contraction of the ventricle.
(1) Aimond F, Rauzier JM, Bony C, Vassort G (2000) J BiolChem 275(50):39110-6.
(2) Hu H, Sachs F (1997). J Mol Cell Cardiol 29(6):1511-23
(3) Kim D (1992) J Gen Physiol 100 1021-1040
(4) Lesage F and Lazdunski M (2000) Am J Physiol 279: F793-F801
(5) Maingret F, Patel AJ, Lesage F, Lazdunski M, Honore E (1999) J Biol Chem;274: 26691-6
(6) Zabel, M., Koller, B.S., Sachs, F. & Franz, M.R. (1996). Cardiovascular Research 32: 120-130.