Transmural differences in rat ventricular protein kinase C epsilon correlate with its functional regulation of a transient cardiac K+ current

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Transmural differences in rat ventricular protein kinase C epsilon correlate with its functional regulation of a transient cardiac K⁺ current

K. S. Thorneloe, X. F. Liu , M. P. Walsh and Y. Shimoni

Department of Biochemistry and Molecular Biology, Canadian Institute of Health Research Group in Regulation of Vascular Contractility and * Department of Physiology and Biophysics , University of Calgary Health Sciences Centre, Calgary, Alberta, Canada

The effects of PKC activation on a transient (I_t) and a sustained (I_ss) cardiac K⁺ current and the subcellular distribution of the epsilon isoform of PKC (PKC $epsilon$ ) were compared in epicardial and endocardial regions of the rat ventricle.
Activation of PKC $epsilon$ with a diacylglycerol analogue (di-octanoyl-glycerol (DiC8), 20 µM) leads to differential effects in epicardial and endocardial cells. In epicardial cells (n = 20) I_t and I_ss are attenuated by 17.7 ± 2.1 % and 11.9 ± 3.1 %, respectively (means ± S.E.M.). In endocardial cells I_t attenuation was significantly smaller (4.6 ± 1.6 %, n = 14, P < 0.0005). I_ss attenuation was similar to that in epicardial cells (10.5 ± 3.8 %).
PKC $epsilon$ expression was measured by Western blotting. Calculated endocardial/epicardial ratios showed no regional differences in total protein extracts (1.04 ± 0.11, mean ± S.E.M, n = 4), but PKC $epsilon$ distribution in the cytosolic fraction showed a marked difference, with significantly (P < 0.05) higher levels in endocardial extracts. The cytosolic endocardial/epicardial PKC $epsilon$ ratio was 2.64 ± 0.24 (n = 4), indicating a reduced amount of PKC $epsilon$ in the membrane fraction of the endocardium. This could account for the reduced effect of DiC8 on I_t in endocardial myocytes.
Under both hypothyroid and streptozotocin-induced diabetic conditions the difference in endocardial and epicardial cytosolic PKC $epsilon$ levels was absent (ratios of 0.86 ± 0.21 (n = 4) and 1.09 ± 0.16 (n = 3), respectively; means ± S.E.M.). Ratios in the total protein extracts were not significantly different from those in control conditions.
The results show transmural differences in the functional effects of PKC $epsilon$ activation on a cardiac K⁺ current, and in the subcellular distribution of PKC $epsilon$ . These differences are absent in diabetic and hypothyroid conditions.

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