Inhibition of the Na +–H + exchanger with cariporide abolishes stretch-induced calcium but not sodium accumulation in mouse ventricular myocytes
We address the question whether activation of the sodium–proton exchanger (NHE) does contribute to the stretch-induced accumulation of intracellular sodium and calcium in mouse ventricular myocytes. NHE-blocker cariporide (10 μM) were applied to the bath for 10 min. Axial stretch was applied for 2 m...
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Published in | Cell calcium (Edinburgh) Vol. 37; no. 1; pp. 69 - 80 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Netherlands
Elsevier India Pvt Ltd
2005
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Subjects | |
Online Access | Get full text |
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Summary: | We address the question whether activation of the sodium–proton exchanger (NHE) does contribute to the stretch-induced accumulation of intracellular sodium and calcium in mouse ventricular myocytes.
NHE-blocker cariporide (10
μM) were applied to the bath for 10
min. Axial stretch was applied for 2
min by increasing the distance between an adherent glass stylus and the patch pipette by 20%. Myocytes (stimulated at 3
Hz) were shock-frozen in diastole and the membrane currents monitored till cryofixation. Controls were treated identically, but not stretched. Total sodium and calcium concentrations ([Na], [Ca] = sum of free and bound Na and Ca) were measured by electron probe microanalysis (EPMA) in peripheral and central cytosol, mitochondria, nucleus and nuclear envelope.
Cariporide did not reduce the stretch-activated negative current. The stretch-induced rise in [Na] was not different in the presence and in the absence of cariporide. Cariporide significantly reduced diastolic [Ca] in the cytosol of stretched myocytes.
Since cariporide does not prevent the stretch-induced [Na] accumulation, we suggest that not NHE but the stretch-activated streptomycin-sensitive current
I
SAC causes the well documented stretch-induced [Na] accumulation. The discovery that cariporide prevents the stretch-induced rise in cytosolic [Ca] demonstrates an important additional effect of the drug on calcium handling. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0143-4160 1532-1991 |
DOI: | 10.1016/j.ceca.2004.06.006 |