Contributions of [Ca2+]i, [Pi]i, and pHi to altered diastolic myocyte tone during partial metabolic inhibition.
Open Access
- 1 July 1991
- journal article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 88 (1), 55-61
- https://doi.org/10.1172/jci115304
Abstract
Ischemia may cause increased or decreased distensibility of the left ventricle, but the cellular mechanisms involved have not been clarified. We examined the possible contributions of changes in intracellular inorganic phosphate, pH, and Ca2+ concentrations to altered diastolic function in cultured myocytes subjected to partial metabolic inhibition. Paced cultured embryonic chick and adult rabbit ventricular myocytes superfused with 20 mM 2-deoxyglucose (2DG) exhibited an increase in end-diastolic intracellular free calcium concentration ([Ca2+]i) and an upward shift in end-diastolic cell position. These results indicate that glycolytic blockade increases diastolic and systolic calcium in paced ventricular myocytes, and that this elevated diastolic calcium influences the extent of diastolic relaxation. In contrast, paced ventricular myocytes superfused with 1 mM cyanide (CN) exhibited a similar increase in end-diastolic [Ca2+]i but a decrease in end-diastolic cell position and amplitude of motion. Although changes in ATP contents were similar in both groups (2DG, -29.9%; CN, -40.1%), alterations of intracellular pH and inorganic phosphate concentrations were different. In 2DG-treated cells, pHi did not decrease significantly (7.18 +/- 0.04 to 7.12 +/- 0.11, n = 14) but in the CN group it decreased markedly within 6 min (7.18 +/- 0.04 to 6.76 +/- 0.11, n = 11, P less than 0.01). Intracellular inorganic phosphate decreased slightly in the 2DG group (-14.8%, NS) but increased in cells exposed to CN (45.7%, P less than 0.02). We conclude that while a prominent increase in diastolic [Ca2+]i occurs in rapidly paced ventricular myocytes exposed to either inhibitors of glycolysis or oxidative phosphorylation, the effects of this increase in [Ca2+]i on diastolic distensibility may be influenced by intracellular accumulation of metabolites that decrease the sensitivity of myofilament to [Ca2+]i.Keywords
This publication has 42 references indexed in Scilit:
- Alterations in cation homeostasis in cultured chick ventricular cells during and after recovery from adenosine triphosphate depletion.JCI Insight, 1988
- Opposite initial effects of supply and demand ischemia on left ventricular diastolic compliance: The ischemia-diastolic paradoxJournal of Molecular and Cellular Cardiology, 1987
- Assessment of techniques for preventing glycolysis in cardiac muscleCardiovascular Research, 1986
- Effects of diltiazem on the energy metabolism of the isolated rat heart submitted to ischaemia: A 31P NMR studyJournal of Molecular and Cellular Cardiology, 1986
- External Na-independent Ca extrusion in cultured ventricular cells. Magnitude and functional significance.The Journal of general physiology, 1986
- Triple control of relaxation: implications in cardiac disease.Circulation, 1984
- Acute displacement of the diastolic pressure-volume curve of the left ventricle: role of the pericardium and the right ventricle.Circulation, 1979
- Early changes in regional and global left ventricular function induced by graded reductions in regional coronary perfusionThe American Journal of Cardiology, 1977
- Effect of angina on the left ventricular diastolic pressure-volume relationship.Circulation, 1977
- Changes in Diastolic Stiffness and Tone of the Left Ventricle During Angina PectorisCirculation, 1974