scholarly journals LANTHANUM IN HEART CELL CULTURE

1972 ◽  
Vol 54 (3) ◽  
pp. 441-455 ◽  
Author(s):  
G. A. Langer ◽  
J. S. Frank
Keyword(s):  
Basement Membrane ◽  
Single Phase ◽  
Phase 1 ◽  
Heart Cell ◽  
Phase System ◽  
Heart Cells ◽  
Exchangeable Ca ◽  
Heart Cell Culture ◽  
Rat Heart Cells ◽  
Cellular Ca

Correlation of the localization of La+++ with its effects on Ca++ exchange in cultured rat heart cells is examined with the use of a recently developed technique. 75% of cellular Ca++ is exchangeable and is completely accounted for by two kinetically defined phases. The rapidly exchangeable phase has a t ½ = 1.15 min and accounts for 1 1 mmoles Ca++/kg wet cells or 43% of the exchangeable Ca++ (cells perfused with [Ca++]o = 1 mM) Phase 2 has a t ½ = 19.2 min and accounts for 1.5 mmoles Ca++/kg wet cells or 57% of the exchangeable Ca++. 0.5 mM [La+++]o displaces 0 52 mmoles Ca++/kg wet cells—all from phase 1—and almost completely abolishes subsequent Ca++ influx and efflux The presence of La+++ in the washout converts the washout pattern to a single phase system with a t ½ = 124 min. The effects upon Ca++ exchange are coincident with abolition of contractile tension but regenerative depolarization of the tissue is maintained Electron microscope localization of the La+++ places it exclusively in the external lamina or basement membrane of the cells. The study indicates that negatively charged sites in the basement membrane play a crucial role in the E-C coupling process in heart muscle

scholarly journals Ability of the orally effective iron chelators dimethyl- and diethyl- hydroxypyrid-4-one and of deferoxamine to restore sarcolemmal thiolic enzyme activity in iron-loaded heart cells

Blood ◽  
1994 ◽  
Vol 83 (9) ◽  
pp. 2692-2697 ◽  
Author(s):  
G Link ◽  
A Pinson ◽  
C Hershko
Keyword(s):  
Enzyme Activity ◽  
Iron Chelation ◽  
Myocardial Cell ◽  
Resting Potential ◽  
Molar Ratio ◽  
Iron Chelators ◽  
Heart Cell ◽  
Heart Cells ◽  
Cell Organelles ◽  
Rat Heart Cells

In view of the profound functional and structural abnormalities shown in our previous studies in cultured, iron-loaded rat heart cells, we have examined the ability of the orally effective iron chelators dimethyl-3-hydroxypyrid-4-one (DMHP or L1) and diethyl-3-hydroxy-pyrid- 4-one (DEHP or CP94) and of deferoxamine (DF) to reverse the damage caused by iron loading to heart cell organelles. At a concentration of 1.0 mmol/L, all three iron chelators were equally efficient in removing iron and restoring the activity of the thiolic sarcolemmal enzymes 5′- nucleotidase and Na,K,ATPase. However, at 0.1 mmol/L DMHP and DEHP were less effective than DF both in their iron-mobilizing effect and in promoting thiolic enzyme recovery. The superior efficiency of DF at low concentrations illustrates the advantage of the hexadentate chelating action of DF as compared with bidentate chelators such as DMHP and DEHP requiring a 3 to 1 molar ratio to iron for optimal effect. In contrast to its beneficial effect on sarcolemmal enzyme activity, iron chelation was unable to reverse the increase in beta-hexosaminidase activity caused by abnormal lysosomal fragility. Our study demonstrates for the first time that iron-induced peroxidative damage to the myocardial cell is associated with a marked loss of Na,K,ATPase activity, an enzyme with a major role in the maintenance of cellular resting potential. The timing of this damage and the restoration of Na,K,ATPase function by iron-chelating treatment suggest a cause-and-effect relationship between the observed injury to the sarcolemmal enzyme and the reversible electrophysiologic abnormalities observed in the same heart culture system in our previous studies.

scholarly journals Role of nerve growth factor in the development of rat sympathetic neurons in vitro. III. Effect on acetylcholine production.

1977 ◽  
Vol 75 (3) ◽  
pp. 712-718 ◽  
Author(s):  
L L Chun ◽  
P H Patterson
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Rat Heart ◽  
Neuronal Survival ◽  
Sympathetic Neurons ◽  
Cell Monolayer ◽  
Heart Cell ◽  
Heart Cells ◽  
Nerve Growth ◽  
Rat Heart Cells

The effect of nerve growth factor (NGF) on the development of cholinergic sympathetic neurons was studied in cultures grown either on monolayers of dissociated rat heart cells or in medium conditioned by them. In the presence of rat heart cells the absolute requirement of neurons for exogenous NGF was partially spared. The ability of heart cells to support neuronal survival was due at least in part to production of a diffusable NGF-like substance into the medium. Although some neurons survived on the heart cell monolayer without added NGF, increased levels of exogenous NGF increased neuronal survival until saturation was achieved at 0.5 microgram/ml 7S NGF. The ability of neurons to produce acetylcholine (ACh) from choline was also dependent on the level of exogenous NGF. In mixed neuron-heart cell cultures, NGF increased both ACh and catecholamine (CA) production per neuron to the same extent; saturation occurred at 1 microgram/ml 7S NGF. As cholinergic neurons developed in culture, they became less dependent on NGF for survival and ACh production, but even in older cultures approximately 40% of the neurons died when NGF was withdrawn. Thus, NGF is as necessary for survival, growth, and differentiation of sympathetic neurons when the neurons express cholinergic functions as when the neurons express adrenergic functions (4, 5).

ICL670A: a new synthetic oral chelator: evaluation in hypertransfused rats with selective radioiron probes of hepatocellular and reticuloendothelial iron stores and in iron-loaded rat heart cells in culture

Blood ◽  
2001 ◽  
Vol 97 (4) ◽  
pp. 1115-1122 ◽  
Author(s):  
Chaim Hershko ◽  
Abraham M. Konijn ◽  
Hans Peter Nick ◽  
William Breuer ◽  
Zvi Ioav Cabantchik ◽  
...  
Keyword(s):  
Synergistic Effect ◽  
Therapeutic Strategies ◽  
Heart Cell ◽  
Heart Cells ◽  
Myocardial Cells ◽  
Iron Stores ◽  
Rat Heart Cells ◽  
Practical Implications ◽  
Iron Excretion

Abstract ICL670A (formerly CGP 72 670) or 4-[3,5-bis-(hydroxyphenyl)-1,2,4-triazol-1-yl]- benzoic acid is a tridentate iron-selective synthetic chelator of the bis-hydroxyphenyl-triazole class of compounds. The present studies used selective radioiron probes of hepatocellular and reticuloendothelial (RE) iron stores in hypertransfused rats and iron-loaded heart cells to define the source of iron chelated in vivo by ICL670A and its mode of excretion, to examine its ability to remove iron directly from iron-loaded myocardial cells, and to examine its ability to interact with other chelators through a possible additive or synergistic effect. Results indicate that ICL670A given orally is 4 to 5 times more effective than parenteral deferoxamine (DFO) in promoting the excretion of chelatable iron from hepatocellular iron stores. The pattern of iron excretion produced by ICL670A is quite different from that of DFO and all iron excretion is restricted to the bile regardless of whether it is derived from RE or hepatocellular iron stores. Studies in heart cell cultures have shown a favorable interaction between DFO and ICL670A manifested in improved chelating efficiency of ICL670A, which is most probably explained by an exchange of chelated iron between ICL670A and DFO. These unique chelating properties of ICL670A may have practical implications for current efforts to design better therapeutic strategies for the management of transfusional iron overload.

scholarly journals Adenosine formation and release from neonatal-rat heart cells in culture

1985 ◽  
Vol 229 (3) ◽  
pp. 799-805 ◽  
Author(s):  
P Meghji ◽  
C A Holmquist ◽  
A C Newby
Keyword(s):  
Rat Heart ◽  
Neonatal Rat ◽  
Heart Cell ◽  
Heart Cells ◽  
Dependent Manner ◽  
Nucleoside Transporter ◽  
Concentration Dependent Manner ◽  
Cells In Culture ◽  
Neonatal Rat Heart ◽  
Rat Heart Cells

The incorporation of [3H]adenosine (10 microM) into neonatal-rat heart cell nucleotides was inhibited in a concentration-dependent manner, such that 50% inhibition was obtained with 0.75 microM-dipyridamole, 0.26 microM-hexobendine or 0.22 microM-dilazep. Adenosine formation was accelerated 2.5-fold to 2.1 +/- 0.3 nmol/10(7) cells in 10 min when cells were incubated with a combination of 30 mM-2-deoxyglucose and 2 micrograms of oligomycin/ml. Of the newly formed adenosine, 6 +/- 2% was in the cells. Dipyridamole, hexobendine or dilazep (10 microM) increased the amount of adenosine in the cells and decreased that in the medium such that 45-50% of the newly formed adenosine was in the cells. Antibodies which inhibited ecto-5'-nucleotidase by 98.7 +/- 0.3% did not alter the rate of adenosine formation or its distribution between cells and medium. We conclude that adenosine was formed in the cytoplasm during catabolism of cellular ATP and was released via the dipyridamole-sensitive symmetric nucleoside transporter.

scholarly journals Ability of the orally effective iron chelators dimethyl- and diethyl- hydroxypyrid-4-one and of deferoxamine to restore sarcolemmal thiolic enzyme activity in iron-loaded heart cells

Blood ◽  
1994 ◽  
Vol 83 (9) ◽  
pp. 2692-2697 ◽  
Author(s):  
G Link ◽  
A Pinson ◽  
C Hershko
Keyword(s):  
Enzyme Activity ◽  
Iron Chelation ◽  
Myocardial Cell ◽  
Resting Potential ◽  
Molar Ratio ◽  
Iron Chelators ◽  
Heart Cell ◽  
Heart Cells ◽  
Cell Organelles ◽  
Rat Heart Cells

Abstract In view of the profound functional and structural abnormalities shown in our previous studies in cultured, iron-loaded rat heart cells, we have examined the ability of the orally effective iron chelators dimethyl-3-hydroxypyrid-4-one (DMHP or L1) and diethyl-3-hydroxy-pyrid- 4-one (DEHP or CP94) and of deferoxamine (DF) to reverse the damage caused by iron loading to heart cell organelles. At a concentration of 1.0 mmol/L, all three iron chelators were equally efficient in removing iron and restoring the activity of the thiolic sarcolemmal enzymes 5′- nucleotidase and Na,K,ATPase. However, at 0.1 mmol/L DMHP and DEHP were less effective than DF both in their iron-mobilizing effect and in promoting thiolic enzyme recovery. The superior efficiency of DF at low concentrations illustrates the advantage of the hexadentate chelating action of DF as compared with bidentate chelators such as DMHP and DEHP requiring a 3 to 1 molar ratio to iron for optimal effect. In contrast to its beneficial effect on sarcolemmal enzyme activity, iron chelation was unable to reverse the increase in beta-hexosaminidase activity caused by abnormal lysosomal fragility. Our study demonstrates for the first time that iron-induced peroxidative damage to the myocardial cell is associated with a marked loss of Na,K,ATPase activity, an enzyme with a major role in the maintenance of cellular resting potential. The timing of this damage and the restoration of Na,K,ATPase function by iron-chelating treatment suggest a cause-and-effect relationship between the observed injury to the sarcolemmal enzyme and the reversible electrophysiologic abnormalities observed in the same heart culture system in our previous studies.

Effects of combined chelation treatment with pyridoxal isonicotinoyl hydrazone analogs and deferoxamine in hypertransfused rats and in iron-loaded rat heart cells

Blood ◽  
2003 ◽  
Vol 101 (10) ◽  
pp. 4172-4179 ◽  
Author(s):  
Gabriela Link ◽  
Prem Ponka ◽  
Abraham M. Konijn ◽  
William Breuer ◽  
Z. Ioav Cabantchik ◽  
...  
Keyword(s):  
Rat Heart ◽  
Chelation Therapy ◽  
Dose Range ◽  
Iron Chelation ◽  
In Vivo Studies ◽  
Heart Cell ◽  
Heart Cells ◽  
Iron Chelation Therapy ◽  
Pyridoxal Isonicotinoyl Hydrazone ◽  
Rat Heart Cells

Abstract Although iron chelation therapy with deferoxamine (DFO) results in improved life expectancy of patients with thalassemia, compliance with parenteral DFO treatment is unsatisfactory, underlining the need for alternative drugs and innovative ways of drug administration. We examined the chelating potential of pyridoxal isonicotinoyl hydrazone (PIH) analogs, alone or in combination with DFO, using hypertansfused rats with labeled hepatocellular iron stores and cultured iron-loaded rat heart cells. Our in vivo studies using 2 representative PIH analogs, 108-o and 109-o, have shown that PIH analogs given orally are 2.6 to 2.8 times more effective in mobilizing hepatocellular iron in rats, on a weight-per-weight basis, than parenteral DFO administered intraperitoneally. The combined effect of DFO and 108-o on hepatocellular iron excretion was additive, and response at a dose range of 25 to 200 mg/kg was linear. In vitro studies in heart cells showed that DFO was more effective in heart cell iron mobilization than all PIH analogs studied. Response to joint chelation with DFO and PIH analogs was similar to an increase in the equivalent molar dose of DFO alone, rather than the sum of the separate effects of the PIH analog and DFO. This finding was most likely the result of iron transfer from PIH analogs to DFO, a conclusion supported directly by iron-shuttle experiments using fluorescent DFO. These findings provide a rationale for the combined, simultaneous use of iron-chelating drugs and may have useful, practical implications for designing novel strategies of iron chelation therapy.

Confocal imaging of calcium in intact ventricular muscle provides a new view of excitation-contraction coupling

1996 ◽  
Vol 54 ◽  
pp. 738-739
Author(s):  
W.G. Wier
Keyword(s):  
Local Control ◽  
Cardiac Tissue ◽  
Cell Function ◽  
Isolated Heart ◽  
Cardiac Cells ◽  
Confocal Imaging ◽  
Ion Concentration ◽  
Heart Cell ◽  
Free Calcium ◽  
Heart Cells

A fundamentally new understanding of cardiac excitation-contraction (E-C) coupling is being developed from recent experimental work using confocal microscopy of single isolated heart cells. In particular, the transient change in intracellular free calcium ion concentration ([Ca2+]i transient) that activates muscle contraction is now viewed as resulting from the spatial and temporal summation of small (∼ 8 μm3), subcellular, stereotyped ‘local [Ca2+]i-transients' or, as they have been called, ‘calcium sparks'. This new understanding may be called ‘local control of E-C coupling'. The relevance to normal heart cell function of ‘local control, theory and the recent confocal data on spontaneous Ca2+ ‘sparks', and on electrically evoked local [Ca2+]i-transients has been unknown however, because the previous studies were all conducted on slack, internally perfused, single, enzymatically dissociated cardiac cells, at room temperature, usually with Cs+ replacing K+, and often in the presence of Ca2-channel blockers. The present work was undertaken to establish whether or not the concepts derived from these studies are in fact relevant to normal cardiac tissue under physiological conditions, by attempting to record local [Ca2+]i-transients, sparks (and Ca2+ waves) in intact, multi-cellular cardiac tissue.

On the Problem of “Two-Phase” Activated Sludge

1991 ◽  
Vol 24 (7) ◽  
pp. 59-64 ◽  
Author(s):  
R. W. Szetela
Keyword(s):  
Activated Sludge ◽  
Single Phase ◽  
Phase System ◽  
Two Phase ◽  
Wastewater Treatment Process ◽  
Sludge Stabilization ◽  
Technological Advantage ◽  
In Series ◽  
State Models ◽  
Activated Sludge Systems

Steady-state models are presented to describe the wastewater treatment process in two activated sludge systems. One of these makes use of a single complete-mix reactor; the other one involves two complete-mix reactors arranged in series. The in-series system is equivalent to what is known as the “two-phase” activated sludge, a concept which is now being launched throughout Poland in conjunction with the PROMLECZ technology under implementation. Analysis of the mathematical models has revealed the following: (1) treatment efficiency, excess sludge production, energy consumption, and the degree of sludge stabilization are identical in the two systems; (2) there exists a technological equivalence of “two-phase” sludge with “single-phase” sludge; (3) the “two-phase” system has no technological advantage over the “single-phase” system.

Sign in / Sign up

Export Citation Format

Share Document