Arachidonic acid and lipoxygenase metabolites uncouple neonatal rat cardiac myocyte pairs

1992 ◽  
Vol 263 (2) ◽  
pp. C494-C501 ◽  
Author(s):  
K. D. Massey ◽  
B. N. Minnich ◽  
J. M. Burt
Keyword(s):  
Arachidonic Acid ◽  
Gap Junctions ◽  
Cardiac Myocyte ◽  
Underlying Mechanism ◽  
Neonatal Rat ◽  
Heart Cells ◽  
Membrane Phospholipids ◽  
Lipoxygenase Pathway ◽  
Rat Heart Cells ◽  
The Right

The effects of arachidonic acid (AA) and its metabolites on the conductance (gj) of the gap junctions between neonatal rat myocardial cells was investigated. AA reduced gj in a dose- (2, 5, and 20 microM) and time-dependent fashion. Pretreatment of the cells with an inhibitor of the 5-lipoxygenase pathway, U-70344A, shifted the dose-response curve to the right; pretreatment with indomethacin, an inhibitor of the cyclooxygenase pathway, had no effect. The mean time to uncoupling was 3.7 +/- 0.3, 3.8 +/- 0.9, and 4.6 +/- 0.6 min (means +/- SE, P less than 0.05) for 5 microM AA, 5 microM AA + indomethacin, and 5 microM AA + U-70344A, respectively. Incorporation of AA into membrane phospholipids was not affected by the inhibitor. These studies suggest that complete uncoupling of the cells occurred at membrane concentrations of 3-4 mol%. The data indicate that AA and a 5-lipoxygenase metabolite uncouple neonatal rat heart cells. The data are discussed with respect to the possible underlying mechanism of uncoupling and the potential role of gap junctions in arrhythmia formation in ischemic heart disease.

Effects of arachidonic acid on the gap junctions of neonatal rat heart cells

1990 ◽  
Vol 417 (2) ◽  
pp. 149-156 ◽  
Author(s):  
Gisela Schmilinsky Fluri ◽  
Anton R�dis�li ◽  
Marius Willi ◽  
Stephan Rohr ◽  
Robert Weingart
Keyword(s):  
Arachidonic Acid ◽  
Gap Junctions ◽  
Rat Heart ◽  
Neonatal Rat ◽  
Heart Cells ◽  
Neonatal Rat Heart ◽  
Rat Heart Cells

Control of gap junction formation in canine trachea by arachidonic acid metabolites

1986 ◽  
Vol 250 (3) ◽  
pp. C495-C505 ◽  
Author(s):  
R. Agrawal ◽  
E. E. Daniel
Keyword(s):  
Arachidonic Acid ◽  
Gap Junctions ◽  
Gap Junction ◽  
Direct Effects ◽  
Leukotriene C4 ◽  
Lipoxygenase Pathway ◽  
Junction Formation ◽  
Acid Metabolites ◽  
Pg E2

This study examined whether the synthesis of the metabolites of arachidonic acid (AA) was involved in gap junction formation by 4-aminopyridine (4-AP) treatment in vitro in canine trachealis. Studies were made of the effects on gap junction formation of putative inhibitors of the cyclooxygenase and of both this and the lipoxygenase pathway of AA metabolism and the direct effects of prostaglandins (PG) E2 and I2. The number of gap junctions of similar size was increased after brief exposure to 4-AP. After indomethacin (IDM), 4-AP treatment decreased the number of gap junctions but did not affect their size. Pretreatment with 5,8,11,14-eicosatetraynoic acid or nordihydroguiaretic acid, putative inhibitors of cyclooxygenase and lipoxygenase enzymes, inhibited both the 4-AP-induced increase and decrease in the number of gap junctions. FPL 55712, a putative antagonist of leukotriene C4, did not alter either the number or the size of gap junctions when added alone or in combination with IDM. AA alone increased the number of gap junctions, but after IDM, AA decreased the number of gap junctions compared with the controls. Incubation of trachealis strips in vitro for 30 min with PGE2 increased the number of gap junctions by about threefold along with an increase in the size of the gap junctions. Similar incubation with PGI2, however, increased the number of gap junctions by approximately 60% without any change in the size. In the course of some control experiments, an interaction between carbachol and alcohol was observed such that alcohol caused an IDM-sensitive relaxation of carbachol-induced contractions, which was not observed when serotonin was the contractile agent. These results strongly suggest that PGE2 and PGI2 increase the formation of gap junctions in canine trachealis and that these prostanoids are released by 4-AP treatment. Leukotrienes may also be inhibitory in the formation of gap junctions, but FPL 55712 did not affect either the increase or the decrease in gap junctions after 4-AP.

Myosin heavy chain turnover in cultured neonatal rat heart cells: effects of [Ca2+]i and contractile activity

1996 ◽  
Vol 271 (5) ◽  
pp. C1447-C1456 ◽  
Author(s):  
K. L. Byron ◽  
J. L. Puglisi ◽  
J. R. Holda ◽  
D. Eble ◽  
A. M. Samarel
Keyword(s):  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Protein Turnover ◽  
Ventricular Myocytes ◽  
Contractile Activity ◽  
Myofibrillar Protein ◽  
Neonatal Rat ◽  
Heart Cells ◽  
Cell Shortening ◽  
Rat Heart Cells

Blockade of L-type Ca2+ channels in spontaneously contracting cultured neonatal rat ventricular myocytes causes contractile arrest, myofibrillar disassembly, and accelerated myofibrillar protein turnover. To determine whether myofibrillar protein turnover. To determine whether myofibrillar atrophy results indirectly from loss of mechanical signals or directly from alterations in intracellular Ca2+ concentration ([Ca2+]i), contractile activity was inhibited with verapamil (10 microM) or 2,3-butanedione monoxime (BDM), and their effects on cell shortening, [Ca2+]i, and myosin heavy chain (MHC) turnover were assessed. Control cells demonstrated spontaneous [Ca2+]i transients (peak amplitude 232 +/- 15 nM, 1-2 Hz) and vigorous contractile activity. Verapamil inhibited shortening by eliminating spontaneous [Ca2+]i transients. Low concentrations of BDM (5.0-7.5 mM) had no effect on basal or peak [Ca2+]i transient amplitude but reduced cell shortening, whereas 10 mM BDM reduced both [Ca2+]i transient amplitude and shortening. Both agents inhibited MHC synthesis, but only verapamil accelerated MHC degradation. Thus MHC half-life does not change in parallel with contractile activity but rather more closely follows changes in [Ca2+]i. [Ca2+]i transients appear critical in maintaining myofibrillar assembly and preventing accelerated MHC proteolysis.

Cation exchange and glycoside binding in cultured rat heart cells

1979 ◽  
Vol 236 (1) ◽  
pp. C87-C95 ◽  
Author(s):  
D. McCall
Keyword(s):  
Neonatal Rat ◽  
Heart Cells ◽  
Turnover Rates ◽  
Ouabain Binding ◽  
Na Pump ◽  
Mammalian Tissues ◽  
Flux Measurements ◽  
The Mean ◽  
Rat Heart Cells ◽  
K Transport

The Na/K-exchange characteristics, ouabain-binding kinetics, and Na pump turnover rates of synchronously contracting monolayers of neonatal rat myocardial cells were studied. The cells exchange Na rapidly (T1/2 = 35 s) with a mean Na flux of approximately 25 (pmol/cm2)/s. The half time (T1/2) of K exchange is much longer (12 min); the mean K flux is 13 (pmol/cm2)/s. Active Na/K transport, as measured by K influx, is relatively ouabain sensitive, and 10(-6) M ouabain produces half-maximal inhibition. Ouabain (10(-2)M) inhibits 60% of the Na efflux and 75% of the K influx. The cells bind [3H]ouabain rapidly (T1/2 = 8 min), but release it very slowly (T1/2 = 11 h), and both the amount bound and the rate of binding were inversely proportional to extracellular K. Specific [3H]ouabain binding demonstrates saturation reaching a maximum of 1.6 x 10(6) molecules per cell at 2 x 10(-7) M [3H]ouabain. From cell surface area and ouabain-sensitive flux measurements, the Na pump density was calculated at 720/micrometer2 with an individual pump turnover rate of 50/s. Thus the studies indicate that despite their neonatal origin, the behavior of the Na pump in these cells is very similar to that in other mammalian tissues.

Chronotropic effect of histamine on cultured neonatal rat heart cells

1979 ◽  
Vol 58 (2) ◽  
pp. 117-123 ◽  
Author(s):  
Klara Csete ◽  
Marie-Claude Auclair ◽  
Paul Lechat
Keyword(s):  
Rat Heart ◽  
Neonatal Rat ◽  
Heart Cells ◽  
Chronotropic Effect ◽  
Neonatal Rat Heart ◽  
Rat Heart Cells

Selective turnover of sarcolemmal phospholipids with lethal cardiac myocyte injury

1990 ◽  
Vol 259 (2) ◽  
pp. C325-C331 ◽  
Author(s):  
Y. Miyazaki ◽  
R. W. Gross ◽  
B. E. Sobel ◽  
J. E. Saffitz
Keyword(s):  
Arachidonic Acid ◽  
Cardiac Myocytes ◽  
Cardiac Myocyte ◽  
Cell Injury ◽  
Specific Radioactivity ◽  
Ischemic Injury ◽  
Phospholipid Metabolism ◽  
Neonatal Rat ◽  
Electron Microscopic ◽  
Electron Microscopic Autoradiography

To delineate the biochemical mechanisms responsible for the transition from reversible to irreversible ischemic injury, we used quantitative electron microscopic autoradiography. Specific alterations of phospholipid catabolism in individual subcellular organelles of cardiac myocytes associated with simulated ischemic injury were identified. Neonatal rat cardiac myocytes were incubated with 5 nM [3H]arachidonic acid to label loci of phospholipid turnover and were exposed to 30 microM iodoacetate to produce reversible and irreversible injury. Although only minute amounts of arachidonic acid were incorporated into sarcolemmal phospholipids under control conditions, 20- and 96-fold increases were observed under conditions leading to reversible and irreversible cell injury, respectively. Increases of 5- and 28-fold in the specific radioactivity of sarcolemmal phospholipids in reversibly and irreversibly injured cells occurred in the absence of significant alterations in the specific radioactivity of other subcellular compartments, demonstrating that accelerated phospholipid catabolism was confined essentially to the sarcolemma. Selective catabolism of sarcolemmal phospholipids, known to be highly enriched in arachidonic acid, is likely to augment local accumulation of arachidonic acid, identified recently as a second messenger regulating myocardial K+ channels. Because the biochemical integrity of the sarcolemma is critical to both electrophysiological function and viability of myocytes, the observed selective alterations of sarcolemmal phospholipid metabolism appear to be pivotal determinants of lethal myocardial injury.

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