The consequences of simulated ischaemia on intracellular Ca2+ and tension in isolated ferret ventricular muscle. 1989

D G Allen, and J A Lee, and G L Smith
Department of Physiology, University College London.

1. In order to study cellular events occurring in ischaemia, we have developed a method for simulating ischaemia in an isolated papillary muscle. Muscles were suspended in a chamber and changed from conventional superfusion with Tyrode solution to gas perfusion with 95% N2/5% CO2 (N2 gas perfusion), thus simultaneously stopping oxygenation and flow. Surface cells of the preparation were injected with the photoprotein aequorin in order to monitor intracellular free calcium concentration [( Ca2+]i). 2. Gas perfusion with 95% O2/5% CO2 (O2 gas perfusion) had little effect on the tension or Ca2+ transients. Superfusion with Tyrode solution equilibrated with 95% N2/5% CO2 (N2 Tyrode) caused tension to decline to 30-40% of control, but had little effect on the amplitude of the Ca2+ transients. N2 gas perfusion caused tension to fall more rapidly and to a lower level than superfusion with N2 Tyrode. Ca2+ transients showed a small initial decline followed by a slowly developing increase in magnitude and duration. 3. Long exposures to N2 gas perfusion caused tension to decline to very low levels and Ca2+ transients to increase to a maximum. After a variable length of time, resting tension began to increase. At approximately the same time, Ca2+ transients began to decrease and eventually disappeared. Resting Ca2+ increased during N2 gas perfusion and remained elevated when the Ca2+ transients had declined. These changes could be reversed by restarting superfusion with standard Tyrode or by perfusion with O2 gas. 4. N2 gas perfusion caused a depolarization of the resting potential and an abbreviation of the action potential. In a long exposure the action potential eventually failed. These changes could be reversed by restarting superfusion with standard Tyrode or by perfusion with O2 gas. 5. Many of the effects of N2 gas perfusion could be mimicked by the addition of 20 mM-lactic acid to the superfusing solution, which caused a profound reduction of tension and also an increase in the amplitude and duration of the Ca2+ transients. Calculation of the changes in intracellular pH caused by the addition of lactic acid suggest that the fall in intracellular pH produced by lactic acid was similar to that occurring in ischaemia. 6. Repeated exposures to N2 gas perfusion caused tension to fall more rapidly and an increased resting tension to develop more rapidly. The slowly developing rise in Ca2+ transients was abolished and a rise in resting Ca2+ occurred more quickly. 7. When muscles were quiescent, exposure to N2 gas perfusion caused an increase in resting light.(ABSTRACT TRUNCATED AT 400 WORDS)

UI MeSH Term Description Entries
D007773 Lactates Salts or esters of LACTIC ACID containing the general formula CH3CHOHCOOR.
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D009200 Myocardial Contraction Contractile activity of the MYOCARDIUM. Heart Contractility,Inotropism, Cardiac,Cardiac Inotropism,Cardiac Inotropisms,Contractilities, Heart,Contractility, Heart,Contraction, Myocardial,Contractions, Myocardial,Heart Contractilities,Inotropisms, Cardiac,Myocardial Contractions
D009584 Nitrogen An element with the atomic symbol N, atomic number 7, and atomic weight [14.00643; 14.00728]. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells.
D010100 Oxygen An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration. Dioxygen,Oxygen-16,Oxygen 16
D010210 Papillary Muscles Conical muscular projections from the walls of the cardiac ventricles, attached to the cusps of the atrioventricular valves by the chordae tendineae. Muscle, Papillary,Muscles, Papillary,Papillary Muscle
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D003327 Coronary Disease An imbalance between myocardial functional requirements and the capacity of the CORONARY VESSELS to supply sufficient blood flow. It is a form of MYOCARDIAL ISCHEMIA (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels. Coronary Heart Disease,Coronary Diseases,Coronary Heart Diseases,Disease, Coronary,Disease, Coronary Heart,Diseases, Coronary,Diseases, Coronary Heart,Heart Disease, Coronary,Heart Diseases, Coronary
D005289 Ferrets Semidomesticated variety of European polecat much used for hunting RODENTS and/or RABBITS and as a laboratory animal. It is in the subfamily Mustelinae, family MUSTELIDAE. Domestic Polecat,Domestic Polecats,European Polecat,European Polecats,Ferret,Mustela putorius,Mustela putorius furo,Polecat, Domestic,Polecat, European,Polecats, Domestic,Polecats, European
D006863 Hydrogen-Ion Concentration The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations

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