TY - JOUR
T1 - The driving force of the Na+/Ca2+-exchanger during metabolic inhibition
AU - Baartscheer, Antonius
AU - Schumacher, Cees A.
AU - Coronel, Ruben
AU - Fiolet, Jan W. T.
PY - 2011
Y1 - 2011
N2 - Objective: Metabolic inhibition causes a decline in mechanical performance and, if prolonged, myocardial contracture and cell death. The decline in mechanical performance is mainly due to altered intracellular calcium handling, which is under control of the Na+/Ca2+-exchanger (NCX) The driving force of the NCX (Delta G(ncx)) determines the activity of NCX. The aim of this study was to describe the relation between Delta G(ncx) and calcium homeostasis during metabolic inhibition. Methods: In left ventricular rabbit myocytes, during metabolic inhibition (2 mmol/L sodium cyanide), sodium ([Na+](i)), calcium ([Ca2+](i)), and action potentials were determined with SBFI, indo-1, and the patch clamp technique. Changes of Delta G(ncx) were calculated. Results: During metabolic inhibition: The first 8 min [Na+] i remained constant, systolic calcium decreased from 532 +/- 28 to 82 +/- 13 nM, diastolic calcium decreased from 121 +/- 12 to 36 +/- 10 nM and the sarcoplasmic reticulum (SR) calcium content was depleted for 85 +/- 3%. After 8 min [Na+](i) and diastolic calcium started to increase to 30 +/- 1.3 mmol/L and 500 +/- 31 nM after 30 min respectively. The action potential duration shortened biphasically. In the first 5 min it shortened from 225 +/- 12 to 153 +/- 11 ms and remained almost constant until it shortened again after 10 min. After 14 min action potential and calcium transients disappeared due to unexcitability of the myocytes. This resulted in an increased of the time average of Delta G(ncx) from 6.2 +/- 0.2 to 7.7 +/- 0.3 kJ/mol during the first 3 min, where after it decreased and became negative after about 15 min. Conclusion: Metabolic inhibition caused an early increase of Delta G(ncx) caused by shortening of the action potential. The increase of Delta G(ncx) contributed to decrease of diastolic calcium, calcium transient amplitude, SR calcium content, and contractility. The increase of diastolic calcium started after Delta G(ncx) became lower than under aerobic conditions
AB - Objective: Metabolic inhibition causes a decline in mechanical performance and, if prolonged, myocardial contracture and cell death. The decline in mechanical performance is mainly due to altered intracellular calcium handling, which is under control of the Na+/Ca2+-exchanger (NCX) The driving force of the NCX (Delta G(ncx)) determines the activity of NCX. The aim of this study was to describe the relation between Delta G(ncx) and calcium homeostasis during metabolic inhibition. Methods: In left ventricular rabbit myocytes, during metabolic inhibition (2 mmol/L sodium cyanide), sodium ([Na+](i)), calcium ([Ca2+](i)), and action potentials were determined with SBFI, indo-1, and the patch clamp technique. Changes of Delta G(ncx) were calculated. Results: During metabolic inhibition: The first 8 min [Na+] i remained constant, systolic calcium decreased from 532 +/- 28 to 82 +/- 13 nM, diastolic calcium decreased from 121 +/- 12 to 36 +/- 10 nM and the sarcoplasmic reticulum (SR) calcium content was depleted for 85 +/- 3%. After 8 min [Na+](i) and diastolic calcium started to increase to 30 +/- 1.3 mmol/L and 500 +/- 31 nM after 30 min respectively. The action potential duration shortened biphasically. In the first 5 min it shortened from 225 +/- 12 to 153 +/- 11 ms and remained almost constant until it shortened again after 10 min. After 14 min action potential and calcium transients disappeared due to unexcitability of the myocytes. This resulted in an increased of the time average of Delta G(ncx) from 6.2 +/- 0.2 to 7.7 +/- 0.3 kJ/mol during the first 3 min, where after it decreased and became negative after about 15 min. Conclusion: Metabolic inhibition caused an early increase of Delta G(ncx) caused by shortening of the action potential. The increase of Delta G(ncx) contributed to decrease of diastolic calcium, calcium transient amplitude, SR calcium content, and contractility. The increase of diastolic calcium started after Delta G(ncx) became lower than under aerobic conditions
U2 - https://doi.org/10.3389/fphys.2011.00010
DO - https://doi.org/10.3389/fphys.2011.00010
M3 - Article
C2 - 21483726
SN - 1664-042X
VL - 2
SP - 10
JO - Frontiers in physiology
JF - Frontiers in physiology
ER -