Gene expression of stretch activated channels and mechanoelectric feedback in the heart

D.A. Saint, W. Liu, J. Tan, Department of Physiology, University of Adelaide, Adelaide, SA, Australia

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.

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