Stretch-modulation of second messengers: effects on cardiomyocyte ion transport.
ABSTRACT In cardiomyocytes, mechanical stress induces a variety of hypertrophic responses including an increase in protein synthesis and a reprogramming of gene expression. Recently, the calcium signaling has been reported to play an important role in the development of cardiac hypertrophy. In this article, we report on the role of the calcium signaling in stretch-induced gene expression in cardiomyocytes. Stretching of cultured cardiomyocytes up-regulates the expression of brain natriuretic peptide (BNP). Intracellular calcium-elevating agents such as the calcium ionophore A23187, the calcium channel agonist BayK8644 and the sarcoplasmic reticulum calcium-ATPase inhibitor thapsigargin up-regulate BNP gene expression. Conversely, stretch-induced BNP gene expression is suppressed by EGTA, stretch-activated ion channel inhibitors, voltage-dependent calcium channel antagonists, and long-time exposure to thapsigargin. Furthermore, stretch increases the activity of calcium-dependent effectors such as calcineurin and calmodulin-dependent kinase II, and inhibitors of calcineurin and calmodulin-dependent kinase II significantly attenuated stretch-induced hypertrophy and BNP expression. These results suggest that calcineurin and calmodulin-dependent kinase II are activated by calcium influx and subsequent calcium-induced calcium release, and play an important role in stretch-induced gene expression during the development of cardiac hypertrophy.
- SourceAvailable from: Patrick Bois[Show abstract] [Hide abstract]
ABSTRACT: The cellular mechanisms that regulate B-type natriuretic secretion are not well elicited. Intracellular fluctuation of calcium ions rate seems to be implicated. In this study, we evaluate the role of ventricular transmembrane calcium channels in the secretion of BNP in normal adult rats (group N) and pressure overload hypertrophied ones (group H). We measured plasma BNP concentration and BNP concentration in culture media of cardiomyocytes from N and H group in the presence and absence of calcium channels antagonists. Plasma BNP concentration was increased in H group in comparison to N group (0.630+/-0.008 ng/ml versus 0.106+/-0.004 ng/ml; p<0.01). This increase in BNP level was also obtained in culture media of H group in comparison to N group (3.45+/-0.7 ng/ml versus 0.53+/-0.22 ng/ml). However, the presence of calcium channels antagonists in the culture media of cardiomyocytes had decreased BNP concentration in both N (nifedipine: 0.22+/-0.04 ng/ml; verapamil: 0.19+/-0.05 ng/ml; diltiazem: 0.17+/-0.03 ng/ml; p<0.05) and H group (nifedipine: 0.18+/-0.05 ng/ml; verapamil: 0.23+/-0.04 ng/ml; diltiazem: 0.28+/-0.1 ng/ml; p<0.05). These results suggest that transmembrane calcium channels may have an important role in the regulation of BNP secretion.Archives of Cardiovascular Diseases 07/2008; 101(7-8):459-63. DOI:10.1016/j.acvd.2008.05.005 · 1.66 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Effects of mechanical stimulation on cardiac electrical activity, gene expression, protein synthesis, and tissue remodelling have received increasing attention in recent years, as reviewed in this issue of PBMB. Little is known, though, about how changes in ventricular filling affect the cell configuration of cardiomyocytes in the ventricular wall. Here, we present first electron-microscopic insight into changes in cardiomyocyte cell structure in situ during acute ventricular volume manipulation. Apart from confirming the anticipated ventricular volume-related changes in cardiomyocyte sarcomere length, there is evidence of (i) unfolding of 'slack' membrane, primarily from sarcolemmal invaginations near the Z-lines, and (ii) stretch-induced incorporation of sub-membrane caveolae into the surface membrane. The functional relevance of these changes in cardiomyocyte membrane configuration-other than to cater for the length-dependent modulation of the cell surface to cell volume ratio-remains to be elucidated.Progress in Biophysics and Molecular Biology 05/2003; 82(1-3):221-7. DOI:10.1016/S0079-6107(03)00024-5 · 3.38 Impact Factor