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A Weisberg

Publications and source records attributed to A Weisberg.

36 records · Page 2Linked to original sources
PubMed1992

Contractile proteins in myocardial cells are regulated by factor(s) released by blood vessels.

The importance of perfusion of the coronary vasculature in the regulation of ATPase activity of myosin in rat myocardial cells has been studied. Quantitative histochemistry was used to determine the activity of the enzyme among cells in tissues that had been either perfused through the coronary system or superfused over the surface of the tissue. Enzymatic activity was measured in cryostatic sections from three different preparations: 1) hearts frozen immediately after removal from the animal; 2) isolated hearts frozen after they had been perfused through the coronary circulation; and 3) isolated papillary muscles or trabeculae that had been superfused after dissection and then frozen. ATPase activity was measured in the isolated tissues at different times after dissection. Both calcium- and actin-activated myosin ATPase activities were uniform among cells in both the ventricles of the hearts frozen immediately after dissection and those that had been perfused through the coronary system. In the superfused tissues, although calcium-activated myosin ATPase activity was uniform, actin-activated ATPase activity was not uniform for about 90 minutes after the dissection, the period required for stabilization of the contraction. The pattern of nonuniformity was complex. In all bundles the lowest enzymatic activity was found in the most superficial cells. In very thin bundles, the cells in the center had the highest activity. In the medium and thicker bundles, there were three concentric zones of actin-activated ATPase activity, the superficial zone with the lowest activity, an intermediate zone with high activity, and a central zone with lower activity. Within each zone, the activity was often greatest in myocardial cells immediately next to blood vessels even though the blood vessels had not been perfused. The transverse distribution of ATPase activity of myosin could be explained by a mechanism in which cells in blood vessels (presumably endothelium) release a substance that upregulates myosin ATPase activity, with the rate of release being related to the local oxygen tension. A downregulating substance may also be produced. The period of stabilization of the contraction coincides with the time during which the pattern of actomyosin ATPase activity is nonuniform. These data suggest that the contractile proteins are regulated by a substance produced by blood vessels in proportion to the local PO2, and possibly in relation to shear force on the vascular endothelium.

Adenosine Triphosphatases↗
PubMed1991

A physiological basis for variation in the contractile properties of isolated rat heart.

1. The maximum Ca(2+)-activated force, maximum velocity of unloaded shortening and both Ca(2+)- and actin-activated ATPase activities of myosin have been measured in detergent-skinned preparations of isolated bundles of rat right ventricle after exposure of the intact tissue to different conditions of superfusion, mechanical activity and temperature. 2. Maximum Ca(2+)-activated force per unit cross-sectional area decreases with increasing cross-sectional area, and, in the absence of electrical stimulation, with the duration of superfusion. Maximum velocity of unloaded shortening is not influenced by these differences. 3. Actin-activated ATPase activity of myosin decreases as cross-sectional area increases and duration of superfusion increases, but the extent of the decrease in enzymatic activity is less than that of developed force. Ca(2+)-activated ATPase activity is independent of these differences. 4. Actin-activated ATPase activity in cryostatic sections of quickly frozen tissue is not uniform across the transverse section. In thin bundles, it is highest in the centre and lowest at the edge of the section, which correspond, respectively, to the centre and the surface of the tissue bundle. Exposure of the tissue section to 1 microM-cyclic AMP increases the actin-activated ATPase activity of myosin with the largest increase in activity occurring at or near the surface of the bundle. 5. Ca(2+)-activated ATPase activity of myosin is uniform across the transverse section and is not changed by cyclic AMP. 6. Electrical stimulation, elevated Ca2+ concentration in the superfusion medium, or isoprenaline partially or completely reverse the decline in maximum Ca(2+)-activated force produced by prolonged superfusion of the bundle before its skinning. 7. These observations are similar in many ways to those made on frog skeletal muscles by Elzinga, Howarth, Rull, Wilson & Woledge (1989a). An explanation based on the existence of a physiological mechanism for regulating the properties of force generators is proposed. Regulation of the attachment of the cross-bridge to an actin filament may be the basis for the regulatory mechanism.

Actins↗
PubMed1991

Blunt splenic injuries: nonsurgical treatment with CT, arteriography, and transcatheter arterial embolization of the splenic artery.

The management and outcome of blunt splenic injury diagnosed with computed tomography (CT) were studied in 44 consecutive patients who were hemodynamically stable or whose condition stabilized rapidly with resuscitation. Celiac and splenic arteriography was used in the triage of patients for nonsurgical treatment or for hemostasis. Patients without arterial extravasation of contrast material at arteriography were treated with bed rest only (group 1, n = 19); patients who had such extravasation were treated with bed rest after percutaneous transcatheter coil occlusion of the proximal splenic artery (group 2, n = 17). Abdominal exploration without angiography or embolotherapy was begun if the patient or attending surgeon did not agree with the treatment protocol (group 3, n = 8). Treatment with bed rest alone was successful in 18 patients. Clinical control of hemorrhage was accomplished in all patients in group 2 and one patient in group 1. Thus, exploratory laparotomy was avoided in 34 of 36 patients (94%) in whom nonoperative management was attempted; splenic salvage was achieved in 35 of 36 patients (97%).

Adult↗
PubMed1991

Effect of left atrial filling pressure on the activity of specific myosin isozymes in rat heart.

One of the fundamental properties of cardiac muscle is the increase in force generated and work performed with a rise in the resting length of the tissue. There are data to indicate that length-dependent responses of electromechanical coupling and calcium binding by troponin are part of the basis for the pressure-volume relation in the heart. In this study, the contribution of changes in the functional properties of the contractile proteins independent of modification in electromechanical coupling has been examined. Isolated working hearts containing either a mixture of myosin heavy chain (MHC) isozymes (alpha[fast] and beta [slow]) or exclusively the fast MHC have been subjected to left atrial filling pressures (LAPs) between 5 and 20 cm H2O. After 40 minutes at a given LAP, the heart was quickly frozen. The relative activities of calcium- and actin-activated ATPase of V1 and V3 myosin, containing alpha- and beta-MHC, were measured in cryostatic sections of the heart by quantitative histochemistry under conditions for which the concentration of calcium would not be limiting. In hearts containing both isozymes of myosin, the relative enzymatic activity of each isozyme of myosin varied with LAP. At low LAP, V1 was primarily responsible for the enzymatic activity, but as LAP increased the relative contribution of V1 decreased and that of V3 increased. The change in the calcium- and actin-activated activities of the enzyme with change in LAP occurred within 5 minutes and was reversible. In spite of the apparent substitution of enzymatic activity of V3 for V1, total myosin ATPase activity did not decline, but instead remained constant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

A calcium independent on-off switch for cardiac force generators.

Developed force and ATPase activity of actomyosin in cardiac muscle are regulated not only by the concentration of cytosolic calcium, but also by the state of the contractile proteins. In this study, it has been shown that cardiac actomyosin ATPase, even in the presence of adequate Ca, can exist in an inactive state. Micromolar cyclic AMP activates the ATPase, inducing substantial enzymatic activity. Both active and inactive forms of myosin can co-exist in the same cells. Mammalian hearts appear to contain a physiological mechanism for altering the response of actomyosin to optimal concentrations of Ca.

Animals↗
PubMed1988

Ca-independent regulation of cardiac myosin.

Calcium-independent regulation of the contractile proteins of cardiac muscle has been studied using hyperpermeable cells from rat ventricles and sections of quickly frozen rat hearts. These preparations have been used to study maximum Ca-activated force, myosin ATPase activity and the maximum velocity of unloaded shortening. Beta adrenergic activity increases the amount of force and the ATPase activity in accordance with the concentration of the V1 isozyme of myosin. V3 activity is decreased at the same time. In tissues containing only V1, there is no change in maximum velocity in response to beta adrenergic stimulation. These results indicate that beta adrenergic stimulation recruits V1 force generators and probably regulates a transition between a Ca unresponsive and a Ca responsive force generator. A 21,000 dalton protein that reproduces the effect of beta adrenergic stimulation on myosin has been isolated.

Adenosine Triphosphatases↗
PubMed1987

Ca-independent regulation of cardiac myosin.

Calcium-independent regulation of the contractile proteins of cardiac muscle has been studied using hyperpermeable cells from rat ventricles and sections of quickly-frozen rat hearts. These preparations have been used to study maximum Ca-activated force, myosin ATPase activity and the maximum velocity of unloaded shortening. Beta adrenergic activity increases the amount of force and the ATPase activity in accordance with the concentration of the V1 isozyme of myosin. V3 activity is decreased at the same time. In tissues containing only V1, there is no change in maximum velocity in response to beta adrenergic stimulation. These results indicate that beta adrenergic stimulation recruits V1 force generators and probably regulates the transition between a Ca unresponsive and a Ca responsive force generator. This type of regulation provides the cell with the ability to operate along many different force-velocity relations.

Adenosine Triphosphatases↗
PubMed1987

Beta-adrenergic regulation of cardiac myosin.

Calcium-independent regulation of the contractile proteins of cardiac muscle has been studied using hyperpermeable cells from rat ventricles and sections of quickly frozen rat hearts. These preparations have been used to study maximum calcium-activated force, myosin ATPase activity, and the maximum velocity of unloaded shortening. Beta-adrenergic activity increases the amount of force and the ATPase activity in accordance with the concentration of the V1 isozyme of myosin. V3 activity is decreased at the same time. In tissues containing only V1, there is no change in maximum velocity in response to beta-adrenergic stimulation. These results indicate that beta-adrenergic stimulation recruits V1 force generators and probably regulates a transition between a calcium unresponsive and a calcium responsive force generator.

Actins↗
PubMed1987

Isozyme specific modification of myosin ATPase by cAMP in rat heart.

The total ATPase activity of myosin and the values for the isozyme V1 have been measured in hearts from rats of different ages and with different levels of thyroid function. The contribution of V3 was calculated from the difference between total and V1 ATPase, neglecting the small contribution of V2. Hearts were quickly frozen after rapid removal from the animals in order to preserve the state of ATPase activity that existed in the intact animal, and ATPase activity was measured in thin sections of tissue by a microphotometric technique. In euthyroid hearts, although cAMP increases total myosin ATPase activity and the activity of V1, the cyclic nucleotide inhibits the ATPase activity of V3. In hearts from rats with developing hypothyroidism following thyroidectomy, the same occurs. After a sufficient period has elapsed after thyroidectomy for V1 to have practically disappeared, cAMP has no effect on ATPase activity, but the injection of thyroid hormone restores the effect. Total myosin ATPase activity is maintained relatively constant as the animal ages from 80 to 165 days and during the first 10-11 days following thyroidectomy even though the concentration of V1 is dropping. The explanation proposed for these observations is that myosin can exist in two different forms, only one of which can participate in the active generation of force. The transition between the two forms is regulated by a soluble factor that is itself controlled by the adrenergic system. The factor(s) involved in this regulatory mechanism is soluble and can be transferred between different thin sections cut from a frozen heart.

Actins↗
PubMed1986

Adrenergic regulation of myosin adenosine triphosphatase activity.

The amount of inorganic phosphate liberated by the adenosine triphosphatase activity of myosin in a thin section of cardiac tissue can be measured quantitatively by precipitation with calcium in an alkaline medium under a defined set of conditions. Specificity of the procedure for myosin adenosine triphosphatase has been confirmed by the response to inhibitors and to different degrees of contractile filament overlap. Precise quantitation of adenosine triphosphatase activity has been demonstrated by (1) constant rate over time, (2) linearity with amount of enzyme, (3) correct values for the Km of adenosine triphosphate, and (4) a similar value for Vmax to those determined by more traditional procedures. Stimulation of the beta-adrenergic system by the release of catecholamines following injection of the animal with 6-hydroxydopamine causes a rise and then a fall of both calcium- and actin-activated adenosine triphosphatase in parallel with the changes in blood levels of the transmitter. Tyramine injection of rats produces a dose related increase in myosin adenosine triphosphatase. Perfusion of isolated hearts with isoproterenol increases myosin adenosine triphosphatase in dose-related manner. Addition of cyclic adenosine monophosphate and phosphodiesterase inhibitor to the solution bathing frozen, dried sections of heart increases both calcium- and actin-activated adenosine triphosphatase activity by almost 150%. The data show that the beta-adrenergic system, through cyclic adenosine monophosphatate, regulates the enzymatic activity of myosin, independent of the concentration of calcium. The possible role of this regulatory mechanism in the physiological modulation of cardiac contractility is discussed.

Actins↗
PubMed1986

The properties of cardiac contractile proteins are modulated by autonomic innervation.

The force generators in myocardial cells of rats and rabbits can exist in three different states: relaxed and calcium unresponsive; relaxed and calcium responsive; and contracted. The transition between the two calcium responsive states is produced by the abrupt rise in the concentration of calcium ions during activation by depolarization of the surface membrane. The transition between the two relaxed states is controlled by the beta-adrenergic system. Stimulation converts calcium unresponsive to calcium responsive force generators by causing the release of a 21,000 dalton regulatory factor from intracellular sites on a membrane. The factor then interacts with myosin. The regulatory system can distinguish between V1 and V3 myosins, producing a calcium responsive state in the former and a calcium unresponsive state in the latter. The result of beta-adrenergic activity is, therefore, an increase in the faster and a decrease in the slower force generators. As a result individual cardiac cells can have many different force-velocity relations.

Animals↗
PubMed1983

Regulation of calcium sensitivity in perforated mammalian cardiac cells.

Sarcolemmal perforations can be produced in bundles of rat right ventricular cells by either perfusion of the heart or soaking of the bundles with a solution containing 10 mM EGTA. All cells are affected and lose approximately 40% of the surface membrane. In these cells it is possible to show cAMP regulation of contractility (maximum Ca-activated force) without cAMP regulation of Ca sensitivity (pCa for 50% of maximum Ca-activated force). Therefore, the target molecule for cAMP is different for the two regulatory systems. Both regulatory systems can be slowly washed out of the cell by 10 mM EGTA solution but not by relaxing or contraction solutions. A model for regulation of Ca sensitivity is proposed.

Animals↗
PubMed1983

Energy transport from mitochondria to myofibril by a creatine phosphate shuttle in cardiac cells.

In hyperpermeable cardiac cells, in which the surface membrane has been made highly permeable to small molecules and ions, resting tension increases when the concentration of ATP falls below 200 microM. Peak resting tension occurs in 10 microM ATP and equals 60% of maximum Ca-activated force in 5 mM ATP. The mitochondria in hyperpermeable cells can maintain an ATP concentration above 200 microM if supplied with O2, substrate, ADP, and inorganic phosphate (Pi). Removal of ATP from the bathing solution does not increase resting tension as long as creatine phosphate is present. However O2, substrate, and Pi cannot lower resting tension in the absence of ATP and creatine phosphate. These results are interpreted as evidence for adenine nucleotide tightly bound to the myofibrils and a creatine phosphate shunt of energy from the mitochondria to the myofibrils.

Adenosine Diphosphate↗
PubMed1983

Regulation of cardiac contractile proteins by phosphorylation.

Several of the contractile proteins of the heart can be phosphorylated, but in studies with isolated proteins only phosphorylation of the inhibitory subunit of troponin (TnI) produces a major change in the properties of the contractile system. As TnI is phosphorylated, the concentration of calcium required for activation of contraction is increased. Phosphorylation of the tropomyosin-binding subunit of troponin (TnT) or of the light chain of myosin fails to change ATPase activity of the isolated protein system. Phosphorylation of TnI is stimulated by the beta-adrenergic system and inhibited by the cholinergic system. Maximum calcium-activated force produced by the contractile system can be increased in hyperpermeable cardiac cells by cyclic AmP (cAMP) or agents that stimulate cAMP synthesis. This change in the contractile system, which appears to be part of the physiological response to beta-adrenergic stimulation, is mediated by phosphorylation of an intermediate that then modifies the contractile system. Phosphorylation of the contractile proteins is not involved.

Adenosine Triphosphate↗
PubMed1982

Histochemical detection of specific isozymes of myosin in rat ventricular cells.

A histochemical method for distinguishing isozymes of myosin in rat ventricles has been developed. The procedure involves preincubation in pH 10.5, which inhibits Ca-activated ATPase of the V3 isozyme but not the V1 isozyme of myosin. The specificity of the technique has been demonstrated by comparison of results in hearts from young euthyroid and hypothyroid rats, in which the predominant isozymes are, respectively, V1 and V3. The technique is capable of detecting as small a change in the relative amount of V1 as 15% of the total myosin. Isoenzymes appear to be uniformly distributed within each ventricular cell. There is only a small difference in the content of V1 among the cells in a ventricular chamber of hearts from young euthyroid and hypothyroid rats, but in the period of rapid transition of isozyme content after thyroidectomy, there is considerable heterogeneity of V1 concentration among the cells. The functional implications of the mixture of isozymes is discussed.

Adenosine Triphosphatases↗