Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In striated muscle the transition from the active to the resting state requires a reduction in the cytosolic concentration of ionized calcium (Ca2+), achieved by a rapid sequestration into the sarcoplasmic reticulum and the return of some Ca2+ to the extracellular phase. Morphologically the sarcoplasmic reticulum (SR) is heterogeneous. Specialized regions occur whenever the limiting membranes of the SR approach those of the plasmalemma. These specializations include a narrowed lumen, relative to that found in non-specialized parts of the SR, the presence of electron-dense 'feet' extending into the junctional gap separating the facing membranes of the plasmalemma and the SR, and the occurrence of intraluminal densities. These specializations can assume a variety of configurations, some of which appear to be species specific. The accumulation of Ca2+ by the SR, is a rapid process and the required energy is derived from the hydrolysis of ATP via a Ca2+-activated ATPase in the limiting membranes of the SR. Impaired relaxation in heart muscle can result either from an inadequate supply of ATP, Ca2+-overload, failure of the Ca2+-activated ATPase enzyme, leakage of Ca2+ from the SR, or the failure of the cell to return Ca2+ back into the extracellular phase. Evidence will be presented to show that the rise in resting tension that is caused by an inadequate supply of oxygen involves a mobilization of Ca2+ from the internal stores, and insufficient ATP to drive the ATPase enzyme in the SR, rather than a malfunction of the enzyme. Likewise ouabain-induced contractures have been found to be associated with diminished tissue stores of ATP, the rise in tissue Ca2+ occurring as a late phenomenon.
Eur J Cardiol 1978 Jun
PMID:Relaxation in heart muscle: some morphological and biochemical considerations. 14 66

Mild pulmonic stenosis in the dog, where right ventricular peak systolic pressure was increased approximately 150% at the time of sacrifice, induced 100% or more increase in right ventricular free wall weight by 3 weeks postoperative. Accompanying cardiac hypertrophy at these postoperative times, there was a decrease in both tissue PO2 levels and cAMP concentrations in the hemodynamically stressed ventricle, the right ventricle. Myosin ATPase activity was elevated as well as the velocity of contractile element shortening. The hemodynamically nonstressed left ventricle did not hypertrophy at these early postoperative times.
Basic Res Cardiol
PMID:Changes in cAMP concentrations during chronic cardiac hypertrophy. 21 47

In the sarcoplasmic reticulum of the myocardium, celular organell which function is to regulate the cytoplasmic concentration of calcium in contraction and relaxation, we have studied the effect of hypertonic solutions of sucrose between 1 and 6.96 times the normal tonicity in order to observe the behavior of the internal linked or free calcium of this structure, as well as to prove the hypothesis that hypertonic solutions encourage the calcium exit of the sarcoplasmatic reticulum with the resulting signs of contractures. The following results were obtained: 1. The ATP hydrolisis and calcium transport rate are 14% and 90% respectively of the maximum speeds of 10(-5) M in calcium, while for concentrations of 10(-7) M or ess of the said cation, the transport rates and the ATPase do not reach 5% of the maximum values. 2. Between 1 and 2.54 times of the normal tonicity the calcium uptake remains between 400 and 500 nmoles of calcium/mg protein/min, the transported amount of calcium varies between 14 and 16 nmoles/mg protein and the rate of the ATP hydrolysis increases a 37% to 0.4 M in sucrose. 3. Between 0.4 and 1.2 M in sucrose of 2.54 to 6.96 times the isotonicity, the calcium transport rate velocity as well as the ATP hydrolisis are strongly inhibited. The vesicles volume minimizes and the amount of linked calcium remains within the control values, proving that the capacity of linking this cathion is independent from sarcoplasmic reticulum volume. These results show that the sarcoplasmic reticulum is involved in the contractures induced by hypertonic solutions in intact cells, since the osmolarity increase produces changes of volume which results in a decrease of the calcium transportation velocity or in an increase of the exit of said cathion.
Arch Inst Cardiol Mex
PMID:[Changes induced by hypertonic solutions in the transportation of calcium by the cardiac reticular sarcoplasma]. 48 67

The increase in intracellular sodium (Nai), resulting from inhibition of the Na/K ATPase by cardiac glycosides, is known to increase calcium influx via Na(+)-Ca2+ exchange, and thereby increase contractility. This increase in intracellular Ca2+ has been related to the development of intracellular acidification and enhanced activity of the Na(+)-H+ exchanger as a measure by the cell to prevent further acidification. Thus, the efflux of the H+ ions results in an additional increase in Nai. This may subsequently lead to an increased rate of Ca2+ influx and therefore to the potentiation of the effects of cardiac glycosides. To assess the role of Na(+)-H+ exchange in the mechanism of ouabain action in the beating heart we used amiloride, a known inhibitor of Na(+)-H+ exchange. Isolated rat hearts were perfused with either ouabain (50 microM) alone (n = 8, Group I), amiloride (1.0 mM) + ouabain (50 microM) (n = 8, Group II), or amiloride (1.0 mM) alone as a control group (n = 4, Group III). 23Na and 31P NMR spectroscopy were used to assess the changes in Nai and intracellular pH (pHi), respectively, while simultaneous and continuous monitoring of left ventricular pressure was carried out. Perfusion with both ouabain alone (Group I) or ouabain + amiloride (Group II), resulted in a time dependent increase in Nai levels, reaching (within 25 mins) a maximum of 200 +/- 7% of control in Group I, and 170 +/- 10% of control in Group II. Concurrently, a mild but significant decrease in pHi was observed in both groups. This decrease, however, was significantly higher in Group II compared to Group I (0.34 pH units vs. 0.19 pH units, respectively; P less than 0.05), suggesting that inhibition of Na(+)-H+ exchange by amiloride limits the recovery from ouabain-induced intracellular acidification. While developed pressure gradually increased in Group I to a maximum of 268 +/- 52% of control, the addition of amiloride in Group II substantially reduced the positive inotropic effect. Ventricular fibrillation (VF) developed in three of the eight hearts in Group I within 10-13 mins after the addition of ouabain. Interestingly, the rate of Nai increase in hearts that sustained VF was significantly higher compared to those without VF (mean slope 10.1 +/- 2.11 vs. 3.9 +/- 1.0, respectively; P less than 0.0001). Ventricular fibrillation did not develop in Group II or III.(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Cell Cardiol 1992 Mar
PMID:Amiloride in ouabain-induced acidification, inotropy and arrhythmia: 23Na & 31P NMR in perfused hearts. 132 Jul 2

Na+,K(+)-ATPase is a major determinant of myocyte homeostasis and excitation-contraction. Cardiac glycosides such as digitalis and ouabain increase the inotropic state of the heart through the inhibition of Na+,K(+)-ATPase. While cardiac glycosides are commonly used in the setting of congestive heart failure, optimal therapy would depend upon an intact Na+,K(+)-ATPase system. Changes in Na+,K(+)-ATPase activity and glycoside receptor density with the development of cardiomyopathy have not been well defined. Accordingly, left ventricular (LV) function and Na+,K(+)-ATPase activity and glycoside binding were examined in 7 pigs with dilated cardiomyopathy and in 7 controls. Dilated cardiomyopathy was produced by pacing induced supraventricular tachycardia (SVT) for 3 weeks at 240 bpm. Left ventricular function was examined by simultaneous echocardiography and catheterization. Left ventricular fractional shortening significantly decreased with SVT (34 +/- 2 vs. 10 +/- 2%, P less than 0.05) and LV diastolic dimension and pressure significantly increased (3.8 +/- 0.3 vs. 5.1 +/- 0.4 cm, and 8 +/- 2 vs. 27 +/- 2 mmHg, respectively, P less than 0.05) as compared to controls. Na+,K(+)-ATPase activity was assayed as potassium dependent p-nitrophenol-phosphatase activity. Glycoside receptor density (Bmax) and affinity (KD) was determined using [3H]-ouabain binding assays. Na+,K(+)-ATPase activity, Bmax, and KD all significantly fell from control values with SVT induced cardiomyopathy (0.64 +/- 0.06 vs. 0.45 +/- 0.12 micrograms pNP/mg/h, 5.5 +/- 0.4 vs. 1.9 +/- 0.4 pmol/mg, and 15 +/- 3 vs. 9 +/- 3 nM, respectively, P less than 0.05). The distribution of Na+,K(+)-ATPase in LV sections taken from control and SVT hearts were examined using immunohistochemical techniques. A patchy distribution of Na+,K(+)-ATPase along the sarcolemma in SVT sections was observed as opposed to a more uniform distribution in control myocytes. There was no observable change in the relative content and distribution of the Na+,K(+)-ATPase isoforms alpha 2 and alpha 3 in the SVT sections as compared to controls. In an additional set of experiments, changes in LV as well as isolated myocyte responsiveness to ouabain were examined. Left ventricular fractional shortening and peak dP/dt were measured following administration of 20-60 micrograms/Kg of ouabain in control (n = 3) and SVT (n = 3) pigs. In the control group, 40 micrograms/Kg caused a 25% in LV fractional shortening and a 60% increase in peak dP/dt from baseline. Cumulative doses of 60 micrograms/Kg in the control pigs resulted in over a 75% increase in peak dP/dt from baseline values.(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Cell Cardiol 1992 Mar
PMID:Myocardial Na+,K(+)-ATPase in tachycardia induced cardiomyopathy. 132 Jul 3

We investigated the susceptibility of sarcolemmal Na+K(+)-ATPase to singlet oxygen. The role of this enzyme is regulation of Na+ concentration and thereby membrane potential. Inhibition of Na+ pump would lead to intracellular Ca2+ overload therefore further aggravating the injury caused by free radicals. Incubation of isolated sarcolemmal vesicles with irradiated rose bengal (150 nM) resulted in 86 +/- 1% inhibition of Na+K(+)-ATPase activity and histidine (25-100 mM) protected the enzyme in a dose-dependent fashion whereas SOD, catalase or mannitol (.OH radical scavenger) did not have any effect. Also, the inhibition of Na+K(+)-ATPase activity was dependent on rose bengal concentration, intensity of irradiation, duration of light exposure, showing that inhibition was directly related to amount of singlet oxygen generated. These results show that singlet oxygen may have significant disruptive effects on sarcolemmal function and may represent an important mechanism by which the oxidative injury to the myocardium induces arrhythmogenesis.
J Mol Cell Cardiol 1992 May
PMID:Singlet oxygen-induced inhibition of cardiac sarcolemmal Na+K(+)-ATPase. 132 12

Cardiac hypertrophy which occurs during chronic mechanical overload is one of the numerous examples of biological adaptation to environmental requirements. As such, it is obtained at random by trial and error, and adaptation represents the sum of various modifications in gene expression, including the shift in isoform of myosin or in iso Na+, K+ ATPase, the decrease in beta-adrenergic and muscarinic receptors, ryanodine channels or SR Ca2+ ATPase densities and the unchanged density in Ca2+ current. Some of these changes are beneficial at the cellular level, but are finally detrimental for the organism as a whole, as is the slowing of Vmax. It was suggested that the calcium homeostasis of the hypertrophied cardiocyte was fragile and that this modified cell was less able to buffer the changes in the intracellular calcium, thus providing a biological basis for the arrhythmogenicity of the hypertrophied heart. These various modifications may provide a new key for future pharmaceutical research.
Basic Res Cardiol 1992
PMID:The membrane proteins of the overloaded and senescent heart. 132 60

The expression of the Na,K-ATPase was studied in both normal and failing human myocardium which was collected within 5 min of cardiac explantation in preparation for orthotopic transplantation or at the time of organ harvest. Abundance of mRNA for all three catalytic alpha subunits of the Na,K-ATPase was analyzed in samples from patients with end-stage heart failure due to either ischemic or dilated cardiomyopathy, as well as from normal controls. Vanadate facilitated 3H-ouabain binding before and after a Digibind wash was analyzed on tissue from a subset of these patients. mRNA analysis demonstrated that all three catalytic Na,K-ATPase alpha subunits were expressed in human heart and that there was no evidence for change in relative expression or abundance induced by disease. The specific digitalis receptor concentration was 760 +/- 58 and 614 +/- 47 pmol/g wet weight in the samples from normal and failing hearts, respectively (p = NS). From these studies it can be concluded that, whereas there is a tendency for a decrease in the number of ouabain receptors in heart failure, there is no significant alteration in the expression of Na,K-ATPase message or protein caused by chronic heart failure.
Basic Res Cardiol 1992
PMID:Na,K-ATPase expression in normal and failing human left ventricle. 132 67

We reinvestigated the issue of whether l-palmitoylcarnitine inhibits the Na/K pump in the heart. The effects of l-palmitoylcarnitine or ouabain on the Na/K pump current were studied with the voltage-clamp technique in isolated guinea-pig ventricular myocytes. In myocytes bathed in Tyrode's solution, l-palmitoylcarnitine shifted the current-voltage relation inward at all potentials between -80 and 20 mV. the "U"-shaped difference current seen in l-palmitoylcarnitine was maximal at -30 mV and declined at potentials more positive and negative than this. Under conditions that minimized time-dependent currents, ouabain or l-palmitoylcarnitine shifted membrane current inward in the presence of 5.4 mM extracellular potassium. Reduction of extracellular potassium to 0 mM for 2 min also shifted membrane current inward. When extracellular potassium was returned to 5.4 mM, the intracellular sodium that had accumulated was extruded and a transient outward current was generated as a result of Na/K pump stimulation. Ouabain or l-palmitoylcarnitine reversibly suppressed this transient outward current and reduced the rate constant for the decline of this current. The ability of l-palmitoylcarnitine to imitate the actions of ouabain on membrane current and on the transient outward current indicates that this amphiphile inhibits the Na/K pump current in guinea-pig ventricular myocytes. This results is consistent with the suppression by l-palmitoylcarnitine of the activity of Na/K ATPase in cardiac sarcolemmal vesicles.
J Mol Cell Cardiol 1992 Jul
PMID:Inhibition of sodium pump by l-palmitoylcarnitine in single guinea-pig ventricular myocytes. 132 55

Although inhibition of Na(+)-K+ ATPase has been described in the diabetic heart, K+ loss from myocardium has not been observed in a canine model of mild diabetes. The finding of tissue Na+ accumulation and a potential relation to alteration of left ventricular inositol as observed in other tissues in diabetes form the basis of this investigation. Diabetes was induced with alloxan in three groups of male mongrel dogs who were studied after 1 yr. In the initial experiment the tissue compartment volumes, determined with intravenous 51Cr EDTA as a marker, were found to be normal. Calculated cell sodium was increased to 32.8 +/- 2.6 mEq/kg cell H2O vs 18.7 +/- 1.1 in controls (p < 0.01). Cell potassium in diabetes was normal. In the second group, myocardial polyols were analyzed by gas-liquid chromatography. Inositol was diminished in diabetes to 0.61 +/- 23 microM/g of left ventricle, vs the respective control levels of 1.9 +/- 0.57 microM/g (p < 0.02). Sorbitol concentration was unaltered. Left ventricular sodium increments were not associated with altered tissue calcium. In group III the hypothesis that inhibition of Na(+)-K+ ATPase in diabetes might not elicit the expected alteration of K+ transport was assessed during intracoronary infusion of acetyl strophanthidin. No difference in cation responses from control was observed. It is postulated that a change in the conformation of Na(+)-K+ ATPase, with high affinity sodium binding sites facing the intracellular compartment, may render sodium less releasable from cell membrane.
Int J Cardiol 1992 Dec
PMID:Myocardial inositol and sodium in diabetes. 133 48


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