The Driving Force of the Na+/Ca2+-Exchanger during Metabolic Inhibition
Open Access
- 1 January 2011
- journal article
- Published by Frontiers Media SA in Frontiers in Physiology
- Vol. 2, 10
- https://doi.org/10.3389/fphys.2011.00010
Abstract
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 (ΔGncx) determines the activity of NCX. The aim of this study was to describe the relation between ΔGncx 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 ΔGncx 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 ΔGncx 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 ΔGncx caused by shortening of the action potential. The increase of ΔGncx contributed to decrease of diastolic calcium, calcium transient amplitude, SR calcium content, and contractility. The increase of diastolic calcium started after ΔGncx became lower than under aerobic conditions.Keywords
This publication has 29 references indexed in Scilit:
- Nonanticoagulant heparin reduces myocyte Na+and Ca2+loading during simulated ischemia and decreases reperfusion injuryAmerican Journal of Physiology-Heart and Circulatory Physiology, 2010
- Effect of Metabolic Inhibition on Couplon Behavior in Rabbit Ventricular MyocytesBiophysical Journal, 2008
- Kinetics of calcium spikes in rat cardiac myocytesThe Journal of Physiology, 2007
- Na + -Ca 2+ Exchange Current and Submembrane [Ca 2+ ] During the Cardiac Action PotentialCirculation Research, 2002
- Cytoplasmic Sodium, Calcium and Free Energy Change of the Na+/Ca2+-Exchanger in Rat Ventricular MyocytesJournal of Molecular and Cellular Cardiology, 1998
- Small Changes of Cytosolic Sodium in Rat Ventricular Myocytes Measured with SBFI in Emission Ratio ModeJournal of Molecular and Cellular Cardiology, 1997
- The Origin of Increased Cytoplasmic Calcium upon Reversal of the Na+/Ca2+-Exchanger in Isolated Rat Ventricular MyocytesJournal of Molecular and Cellular Cardiology, 1996
- Intracellular [Ca2+] and Vo2 after manipulation of the Free-energy of the Na+/Ca2+-exchanger in isolated rat ventricular myocytesJournal of Molecular and Cellular Cardiology, 1995
- Can Ca entry via Na-Ca exchange directly activate cardiac muscle contraction?Journal of Molecular and Cellular Cardiology, 1988
- The cytoplasmic free energy of ATP hydrolysis in isolatedrod-shaped rat ventricular myocytesJournal of Molecular and Cellular Cardiology, 1988