TY - JOUR
T1 - Protective effect of HOE642, a selective blocker of Na+-H+ exchange, against the development of rigor contracture in rat ventricular myocytes
AU - Ruiz-Meana, Marisol
AU - Garcia-Dorado, David
AU - Juliá, Margarita
AU - Inserte, Javier
AU - Siegmund, Berthold
AU - Ladilov, Yuri
AU - Piper, Michael
AU - Tritto, Francesco Paolo
AU - González, Miguel A.
AU - Soler-Soler, J.
PY - 2000/1
Y1 - 2000/1
N2 - The objective of this study was to investigate the effect of Na+-H+ exchange (NHE) and HCO3--Na+ symport inhibition on the development of rigor contracture. Freshly isolated adult rat cardiomyocytes were subjected to 60 min metabolic inhibition (MI) and 5 min re-energization (Rx). The effects of perfusion of HCO3- or HCO3--free buffer with or without the NHE inhibitor HOE642 (7 μM) were investigated during MI and Rx. In HCO3--free conditions, HOE642 reduced the percentage of cells developing rigor during MI from 79 ± 1% to 40 ± 4% (P < 0.001) without modifying the time at which rigor appeared. This resulted in a 30% reduction of hypercontracture during Rx (P < 0.01). The presence of HCO3- abolished the protective effect of HOE642 against rigor. Cells that had developed rigor underwent hypercontracture during Rx independently of treatment allocation. Ratiofluorescence measurement demonstrated that the rise in cytosolic Ca2+ (fura-2) occurred only after the onset of rigor, and was not influenced by HOE642. NHE inhibition did not modify Na+ rise (SBFI) during MI, but exaggerated the initial fall of intracellular pH (BCEFC). In conclusion, HOE642 has a protective effect against rigor during energy deprivation, but only when HCO3--dependent transporters are inhibited. This effect is independent of changes in cytosolic Na+ or Ca2+ concentrations.
AB - The objective of this study was to investigate the effect of Na+-H+ exchange (NHE) and HCO3--Na+ symport inhibition on the development of rigor contracture. Freshly isolated adult rat cardiomyocytes were subjected to 60 min metabolic inhibition (MI) and 5 min re-energization (Rx). The effects of perfusion of HCO3- or HCO3--free buffer with or without the NHE inhibitor HOE642 (7 μM) were investigated during MI and Rx. In HCO3--free conditions, HOE642 reduced the percentage of cells developing rigor during MI from 79 ± 1% to 40 ± 4% (P < 0.001) without modifying the time at which rigor appeared. This resulted in a 30% reduction of hypercontracture during Rx (P < 0.01). The presence of HCO3- abolished the protective effect of HOE642 against rigor. Cells that had developed rigor underwent hypercontracture during Rx independently of treatment allocation. Ratiofluorescence measurement demonstrated that the rise in cytosolic Ca2+ (fura-2) occurred only after the onset of rigor, and was not influenced by HOE642. NHE inhibition did not modify Na+ rise (SBFI) during MI, but exaggerated the initial fall of intracellular pH (BCEFC). In conclusion, HOE642 has a protective effect against rigor during energy deprivation, but only when HCO3--dependent transporters are inhibited. This effect is independent of changes in cytosolic Na+ or Ca2+ concentrations.
UR - https://www.scopus.com/pages/publications/6744242007
U2 - 10.1111/j.1469-445X.2000.01908.x
DO - 10.1111/j.1469-445X.2000.01908.x
M3 - Article
C2 - 10662888
AN - SCOPUS:6744242007
SN - 0958-0670
VL - 85
SP - 17
EP - 25
JO - Experimental Physiology
JF - Experimental Physiology
IS - 1
ER -