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 microM) 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.
Kondratev
Denis
D
Julius Bernstein Institute of Physiology, University of Halle, Magdeburger Strasse 6, D-06097 Halle, Germany.
Christ
Andreas
A
Gallitelli
Maria Fiora
MF
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D003971:Diastole / Q000187:drug effects / Q000502:physiology; D006146:Guanidines / Q000494:pharmacology*; D006352:Heart Ventricles / Q000166:cytology; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D012964:Sodium / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013314:Stress, Mechanical; D013450:Sulfones / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C093373:cariporide; D012964:Sodium; D002118:Calcium