Direct evidence of changes in myofilament responsiveness to Ca2+ during hypoxia and reoxygenation in myocardium.
In the presence of 1 microM ryanodine, muscles loaded with the calcium indicator aequorin were stimulated at 15-20 Hz to produce steady levels of force and intracellular Ca2+ concentrations [( Ca2+]i) at various extracellular Ca2+ concentration ([Ca2+]o). After 5, 10, and 15 min of hypoxia and 3 min of reoxygenation, tetani were initiated. Force vs. [Ca2+]i relation was shifted to the right 0.11, 0.18, and 0.24 pCa units, and maximal force was down 66, 48, and 37% after start of hypoxia. During reoxygenation, the relationship was shifted up by 26%. In skinned fiber preparations, an increase in inorganic phosphate ion concentration from 0 to 10 mM and 15 mM decreased maximal force development by 32 and 53%, respectively, and shifted the pCa-force curve to the right by 0.08 and 0.14 pCa. A decrease in pH from 7.1 to 6.8 shifted the pCa-force curve to the right by 0.20 pCa units without affecting maximal force. These changes indicate that during hypoxia, a decrease in the sensitivity of the myofilaments to Ca2+ and a depression of maximal Ca2(+)-activated force occur, whereas during reoxygenation, there is an increase in maximal Ca2(+)-activated force.
Hajjar
R J
RJ
Charles A. Dana Research Institute, Boston, Massachusetts.
Gwathmey
J K
JK
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D005289:Ferrets; D006652:Histological Techniques; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D009210:Myofibrils / Q000502:physiology*; D009994:Osmolar Concentration; D010101:Oxygen Consumption; D010710:Phosphates / Q000378:metabolism; D012433:Ryanodine / Q000494:pharmacology
D010710:Phosphates; D012433:Ryanodine; D002118:Calcium