Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The content of the sarcoplasmic reticulum (SR) Ca(2+)-ATPase, transverse tubule dihydropyridine receptor (DHPR), and SR ryanodine receptor (RyR) was determined in muscle of pigs homozygous for the normal RyR allele and homozygous or heterozygous for the malignant hyperthermia-susceptible (MHS) RyR allele. Total muscle membranes isolated from 1-day-old pigs of the three different genotypes did not differ in the content of any of these proteins. However, at 28 days of age, crude membranes and total muscle homogenates from homozygous MHS pigs exhibited only 61-81% of the [3H]PN 200-110 or [3H]ryanodine binding of identical preparations isolated from normal pigs; these MHS membranes also contained only 50% of the normal content of each of the DHPR subunits. The crude membranes and muscle homogenates from heterozygous pigs were intermediate to both types of homozygotes in terms of [3H]PN 200-110 binding, [3H]ryanodine binding, and the content of the DHPR subunits. However, membrane preparations enriched in triadic junctional proteins isolated from 3- to 4-mo-old pigs of the three different genotypes did not differ in their [3H]PN 200-110 binding, [3H]ryanodine binding, or Ca(2+)-ATPase activities. We conclude that, although the stoichiometry of the RyR to DHPR is not altered, the presence of the MHS RyR allele during muscle development results in a decreased relative content of these two proteins. This is probably due to a lower junctional membrane content and may be an important ultrastructural consequence of the altered sarcoplasmic Ca2+ regulation in MHS muscle.
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PMID:Skeletal muscle junctional membrane protein content in pigs with different ryanodine receptor genotypes. 804 87

A transient rise in cytoplasmic Ca2+ activity in the sea urchin egg occurs during fertilization due to release from an intracellular store. Two intracellular receptor Ca2+ channels for inositol 1,4,5-trisphosphate (IP3) and ryanodine have been identified by physiological and immunological techniques. While IP3 is the endogenous messenger for the IP3 receptor, a corresponding physiological messenger for the ryanodine receptor is unknown. A variety of recent experimental evidences suggest that cyclic ADP ribose (cADPR) may be a possible candidate. In this study using both egg homogenates and intact eggs, we show that subthreshold concentrations of cADPR and ryanodine can act synergistically to potentiate Ca2+ release. Addition of 10-20 nM cADPR, which causes little net increase in Ca2+, generally enhances the action of subthreshold concentrations of ryanodine. Similarly the addition of 60-80 microM ryanodine causes a slight transient increase but potentiates maximal Ca2+ increase by a subsequent subthreshold addition of cADPR. While the target of Ca2+ release by ryanodine and cADPR may be the ryanodine receptor, their actions appear to be different and more complex than simply opening the release mechanism. There are significant differences in the kinetics of release by the two agonists. In addition we used a poorly metabolized analog of IP3 and an inhibitor of endoplasmic reticulum Ca2+ ATPase activity, to show that the unfertilized egg contains a rapidly filled Ca2+ store, which is commonly released by both IP3-mediated and ryanodine-mediated release mechanisms.
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PMID:Synergistic calcium release in the sea urchin egg by ryanodine and cyclic ADP ribose. 817 65

We have investigated the molecular basis of the Crooked Neck Dwarf (cn) mutation in embryonic chickens. Using biochemical and pharmacological techniques we are unable to detect normal alpha ryanodine receptor (RyR) protein in intact cn/cn skeletal muscle. Extremely low levels of alpha RyR immunoreactivity can be observed in mutant muscles, but the distribution of this staining differs from that in normal muscle and colocalizes with the rough endoplasmic reticulum immunoglobulin binding protein, BiP. This suggests the existence of an abnormal alpha RyR protein in mutant muscle. In day E12 cn/cn muscle the levels of RyR mRNA are reduced by approximately 80%, while the levels of other muscle proteins, including the alpha 1 subunit of the dihydropyridine receptor, the SR Ca(2+)-ATPase, calsequestrin, and glyceraldehyde-3-phosphate dehydrogenase, and their associated mRNAs are essentially normal in cn/cn muscle. There is also a failure to express alpha RyR in cn/cn cerebellar Purkinje neurons. Expression of the beta RyR, a second RyR isoform, is not initiated in normal skeletal muscle until day E18. In cn/cn skeletal muscle significant muscle degeneration has occurred by this time and the beta RyR is found at low levels in only a subset of fibers suggesting the reduced levels of this isoform are a secondary consequence of the mutation. The cardiac RyR isoform is found in cn/cn cardiac muscle, which contracts in a vigorous manner. In summary, a failure to make normal alpha RyR receptor appears to be an event closely associated with the cn mutation and one which may be largely responsible for development of the cn/cn phenotype in embryonic skeletal muscle.
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PMID:Failure to make normal alpha ryanodine receptor is an early event associated with the crooked neck dwarf (cn) mutation in chicken. 821 59

The Crooked Neck Dwarf (cn) mutation in chickens causes marked changes in intact embryonic skeletal muscle. We have investigated whether the cn/cn phenotype develops in vitro, and if cultured muscle cells are suitable for studies of this mutation. The properties of cn/cn muscle cells maintained in low density primary cultures (6.25 x 10(3) cells/cm2) are described in this report. In normal muscle cells, the alpha ryanodine receptor (RyR) isoform appears prior to, and at greater levels than, the beta RyR, and is detected in mononucleated myocytes. The beta RyR isoform appears within 24 hr after the initiation of myotube formation, which is earlier than anticipated from studies with intact embryonic muscle. Normal alpha RyR protein is not detected in cultured cn/cn muscle cells, whereas the beta RyR, the alpha 1-subunit of the dihydropyridine receptor, the sarcoplasmic reticulum Ca(2+)-ATPase, and calsequestrin are expressed at comparable levels in normal and mutant muscle cells. Calcium transients elicited by electrical stimulation, acetylcholine, and caffeine are similar in normal and cn/cn cultured myotubes and are blocked by ryanodine in both cell types. In addition, comparable L- and T-type calcium currents are observed in normal and mutant muscle cells, suggesting that both the alpha 1-subunit of the dihydropyridine receptor and the beta RyR in mutant muscle cells are functional. Normal and cn/cn muscle cells proliferate and form myotubes in a similar manner. These latter events do not appear to depend on sarcoplasmic reticulum calcium release, as they also occur in normal muscle cells in which calcium release is prevented by chronic treatment with 100 microM ryanodine. Both cn/cn and ryanodine-treated normal muscle cells exhibit morphological changes similar to those observed in intact cn/cn skeletal muscle. Thus, the mutant phenotype observed in ovo is partially expressed under low density culture conditions, and neither beta RyR protein nor its function appear to be capable of preventing the associated changes.
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PMID:Crooked neck dwarf (cn) mutant chicken skeletal muscle cells in low density primary cultures fail to express normal alpha ryanodine receptor and exhibit a partial mutant phenotype. 821 60

The sarcoplasmic reticulum (SR) membranes of rabbit skeletal muscle were allowed to react with N-(3-pyrene)maleimide (PMI) at pH 7 at 30 degrees C. The Ca(2+)-transporting activity of the SR membranes was reduced to 20% when PMI was bound to the extent of 1 mol/mol of Ca(2+)-transporting ATPase. The ATPase and the E-P forming activities were not affected by the binding of PMI up to 2 mol/mol ATPase, indicating that PMI somehow uncoupled Ca(2+)-transport from ATP splitting. Permeability of the SR membranes to Ca2+ ions was increased in parallel with the loss of the Ca(2+)-transporting activity. Of several components of the SR membranes which are reactive with PMI, the ATPase protein was the only one whose modification by PMI was directly related to the loss of the Ca(2+)-transporting activity. Similar results were obtained with the light SR membrane fraction, which lacks the ryanodine receptor, a well-recognized Ca2+ channel. These results indicated that a Ca2+ channel that would have been latent or properly regulated in native ATPase somehow escaped from the normal control mechanism as a result of modification of its SH groups by PMI and went into runaway operation. The activated channel was specific for alkaline earth metal ions, so permeability to other solutes including Co2+, Ni2+, and sucrose remained unchanged after treatment with PMI.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Uncoupling of ATP splitting from Ca(2+)-transport in Ca(2+)-transporting ATPase of the sarcoplasmic reticulum as a result of modification by N-(3-pyrene)maleimide: activation of a channel with a specificity for alkaline earth metal ions. 826

Cobra snake venom cardiotoxins and bee venom melittin share a number of pharmacological properties in intact tissues including hemolysis, cytolysis, contractures of muscle, membrane depolarization and activation of tissue phospholipase C and, to a far lesser extent, an arachidonic acid-associated phospholipase A2. The toxins have also been demonstrated to open the Ca2+ release channel (ryanodine receptor) and alter the activity of the Ca(2+)+Mg(2+)-ATPase in isolated sarcoplasmic reticulum preparations derived from cardiac or skeletal muscle. However, a relationship of these actions in isolated organelles to contracture induction has not yet been established. The toxins also bind to and, in some cases, alter the function of a number of other proteins in disrupted tissues. The most difficult tasks in understanding the mechanism of action of these toxins have been dissociating the primary from secondary effects and distinguishing between effects that only occur in disrupted tissues and those that occur in intact tissue. The use of cardiotoxin and melittin fractions contaminated with trace ('undetectable') amounts of venom-derived phospholipases A2 has continued to be common practice, despite the problems associated with the synergism between the toxins and enzymes and the availability of methods to overcome this problem. With adequate precautions taken with regard to methodology and interpretation of results, the cobra venom cardiotoxins and bee venom melittin may prove to be useful probes of a number of cell processes, including lipid metabolism and Ca2+ regulation in skeletal and cardiac muscle.
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PMID:Possible mechanisms of action of cobra snake venom cardiotoxins and bee venom melittin. 834 68

The subcellular distribution of the Ca(2+)-release channel/ryanodine receptor in adult rat papillary myofibers has been determined by immunofluorescence and immunoelectron microscopical studies using affinity purified antibodies against the ryanodine receptor. The receptor is confined to the sarcoplasmic reticulum (SR) where it is localized to interior and peripheral junctional SR and the corbular SR, but it is absent from the network SR where the SR-Ca(2+)-ATPase and phospholamban are densely distributed. Immunofluorescence labeling of sheep Purkinje fibers show that the ryanodine receptor is confined to discrete foci while the SR-Ca(2+)-ATPase is distributed in a continuous network-like structure present at the periphery as well as throughout interior regions of these myofibers. Because Purkinje fibers lack T-tubules, these results indicate that the ryanodine receptor is localized not only to the peripheral junctional SR but also to corbular SR densely distributed in interfibrillar spaces of the I-band regions. We have previously identified both corbular SR and junctional SR in cardiac muscle as potential Ca(2+)-storage/Ca(2+)-release sites by demonstrating that the Ca2+ binding protein calsequestrin and calcium are very densely distributed in these two specialized domains of cardiac SR in situ. The results presented here provide strong evidence in support of the hypothesis that corbular SR is indeed a site of Ca(2+)-induced Ca2+ release via the ryanodine receptor during excitation contraction coupling in cardiac muscle. Furthermore, these results indicate that the function of the cardiac Ca(2+)-release channel/ryanodine receptor is not confined to junctional complexes between SR and the sarcolemma.
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PMID:The Ca2+-release channel/ryanodine receptor is localized in junctional and corbular sarcoplasmic reticulum in cardiac muscle. 838 86

It has become clear that calcium is an important mediator in the transduction of signals due to ligand binding to cell surface receptors. Cytosolic calcium is typically maintained at low levels in both muscle and non-muscle cells and intracellular sequestering of calcium appears to be important in this process. The identification of intracellular calcium pools has been the subject of much recent study, and it has been proposed that such pools would contain three components: a calcium-activated pump or Ca(2+)-ATPase, a calcium channel such as the inositol trisphosphate receptor or ryanodine receptor, and a high-capacity calcium-binding protein such as calsequestrin or calreticulin. We report here on the localization of two components, the organellar Ca(2+)-ATPase (SERCA) and calreticulin, in neuronal tissues. Using immunofluorescence and subcellular fractionation, we have found that for the most part, these two proteins do not co-localize in neuron cell bodies, dendrites, or axons; but may co-localize at the axon terminal.
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PMID:Differences in the subcellular localization of calreticulin and organellar Ca(2+)-ATPase in neurons. 838 14

We determined the contents of L-type calcium channels (LCC) and other membrane proteins in ventricular homogenates and microsomes prepared from hearts of 30- to 70-day-old Syrian cardiomyopathic (Bio 14.6) and normal hamsters. Quantitative immunoblot assay revealed that myopathic microsomes, as compared with normal controls, were enriched about twofold with the alpha 1-subunit of LCC, the ryanodine receptor calsequestrin, and Na(+)-K(+)-adenosinetriphosphatase (ATPase), whereas the contents of these proteins in ventricular homogenates were not different. In contrast, Na(+)-H+ antiporter and sarcoplasmic reticulum (SR) Ca(2+)-ATPase showed no difference in their contents in both homogenates and microsomes. Radioligand binding assay further showed no significant difference in the number of binding sites for [3H]prazosin, [125I]iodocyanopindolol, and [3H]saxitoxin between myopathic and normal microsomes. These result suggest that whereas membrane densities of LCC and the other proteins examined are not increased in myopathic cardiomyocytes, T-tubule/junctional SR membranes are more easily extracted from them by mechanical disruption. This, together with 1.5-fold higher yield of microsomal fractions from myopathic heart muscle, shows that abnormality exists in the mechanical property of cell membrane in the myopathic heart.
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PMID:Increased mechanical extraction of T-tubule/junctional SR from cardiomyopathic hamster heart. 838 55

The distributions of ryanodine receptor-like immunoreactivity and Ca-ATPase-like immunoreactivity were identified in the guinea-pig and rat central nervous system using antibodies raised against the rabbit skeletal muscle ryanodine receptor and Ca-ATPase. In both guinea-pig and rat cerebellum, the ryanodine receptor-like immunoreactivity was restricted to the soma and dendrites of Purkinje cells. In the medulla, neuron somata in the hypoglossal nucleus were stained in both species, but in the dorsal motor nucleus of the vagus somata were stained in guinea-pigs but not in rats. This species difference in ryanodine receptor-like immunoreactivity is consistent with the species difference in expression of a ryanodine sensitive, calcium activated potassium conductance in neurons of the dorsal motor nucleus of the vagus. Immunoreactivity to Ca-ATPase was present in vagal motoneurons in both species with denser staining in the guinea-pig. The data further support the idea that, in neurons of the dorsal motor nucleus of the vagus, release of intracellular calcium stores via a ryanodine receptor activates a specific class of potassium channels, thereby modulating cell excitability.
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PMID:Distribution of ryanodine receptor-like immunoreactivity in mammalian central nervous system is consistent with its role in calcium-induced calcium release. 839 Jun 24


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