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)

Ion-transporting Na,K-ATPase plays an essential role in nerve conduction. To clarify the cytochemical effects of reserpine on transport Na,K-ATPase activity, the localization of ouabain-sensitive, K(+)-dependent p-nitrophenylphosphatase (K-NPPase) activity was investigated in the facial nerves of normal and reserpinized guinea pigs using a cerium-based method. In the normal facial nerve, the reaction product of K-NPPase activity was observed on the internodal axolemma and Schmidt-Lanterman incisures. In the Ranvier nodes, enzyme activity was localized to the paranodal and nodal axolemma. In the reserpinized nerves, reaction product was detectable on the nodal axolemma but was undetectable on the other parts of the axolemma. Nodal K-NPPase was not affected by reserpine treatment. Therefore, the transport Na,K-ATPase on the nodal axolemma might differ from that on the other parts of the axolemma. Allowing reserpinized animals to survive. Two different ouabain-sensitive K-NPPase reactivities, "reserpine-sensitive" and "reserpine-resistant," might be present in the facial nerve of guinea pigs.
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PMID:Cytochemical localization of ouabain-sensitive, K(+)-dependent p-nitrophenylphosphatase activity in the facial nerve of reserpinized guinea pigs. 926 73

Clinical electrophysiological effects of magnesium (Mg2+) are known for more than 60 years. Mg2+ is a cation to be found ubiquitously in the human body and is involved in more than 300 different enzymatic reactions. However, so far this ion has not been established as a standard therapeutic tool for the treatment of supraventricular tachyarrhythmia. This may be explained by the inconsistent efficacy of Mg2+, partly in relationship to a given plasma Mg(2+)-concentration, partly caused by the uncertainty regarding the dosage and injection rate or the unawareness of the clinical effects of the cation. Mg2+ influences myocardial metabolism by its effects on contractility and electrical activity. Both effects are closely linked. About 12% of cardiac Mg2+ is found in the mitochondria and 2 to 3% in the myofibrils. A large portion is incorporated in adenosin mono-, di- and triphosphate. Mg2+ affects intracellular calcium by inhibiting the influx of calcium into the myocyte through sarcolemmal channels, by modulation of cyclic AMP and by competing with calcium for binding to a single high affinity site on actin. Mg2+ has been linked to a naturally occurring calcium channel blocker. Furthermore Mg2+ blocks the outward current through some potassium channels resulting in an inward rectification of these channels. This suggests that internal magnesium functions as a potassium channel-blocking agent. Early afterdepolarizations are oscillations in the membrane potential and lead to triggered activity and therefore are the electrophysiological substrate of "torsade de pointes" type of ventricular flutter. Mg2+ is able to inhibit both early afterdepolarizations and tachyarrhythmias. Additionally Mg2+ interferes with the sodium-potassium-ATPase system by stabilizing the transmembrane gradient of both cations. Mg2+ deficiency alters this balance and leads to increased neuromuscular excitability. Digitalis is able to block the sodium-potassium-ATPase system, which can be cancelled by Mg2+. Thus the first clinical reports of the therapeutic use of Mg2+ refer to digitalis-induced atrial arrhythmia and ventricular ectopy which could be converted to sinus-rhythm or suppressed by the intravenous application of Mg2+ in 1935. Some years later, the first successful termination of paroxysmal supraventricular and ventricular tachycardia following application of 1.5 to 3 g of Mg2+ was published. But only in the late eighties, systematic studies of the electrophysiological effects of Mg2+ were performed and clinical use was first tested in random fashion in the nineties. Summarizing studies in older patients with different heart diseases and young healthy volunteers the most pronounced and clinically important effect seems to be related to the modulation of the AV node function. The prolongation of the PR interval by 7 to 12% without changing significantly heart rate, QRS duration and QT duration, can be considered a consistent and reproducible effect of Mg2+. In electrophysiological studies a prolongation of the AH interval by 8 to 18%, of the Wenckebach cycle length by up to 20% and of the refractory period of the AV node by 6 to 20% is usually observed, but no change of the retrograde conduction, or the HV interval can be found. Furthermore sinus node recovery time increases by 10% and sinuatrial conduction time by up to 25%. There is no significant effect on intraventricular conduction and atrial and ventricular refractory period. Additionally no significant effect on the anterograde and retrograde refractory period of accessory pathways could be measured; however in some cases (up to 40%) an anterograde block in the accessory pathway may be observed after intravenous Mg(2+)-injection. For the treatment of paroxysmal atrioventricular tachycardia like AV-nodal reentrant tachycardia or orthodromic atrioventricular reentrant tachycardia in WPW syndrome, Mg2+ has been applied in a limited number of recent prospective but uncontrolled studies. Recently, an
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PMID:[Clinico-electrophysiologic effects of magnesium, especially in supraventricular tachycardia]. 933 91

Recent work in animal models of human diffuse axonal injury has generated the hypothesis that, rather than there being physical disruption of the axolemma at the time of injury, a pertubation of the membrane occurs, which leads, over time, to a dysfunction of the physiology of the axolemmal. This dysfunction is posited to lead to a disruption of ionic homeostasis within the injured axon, leading to secondary axotomy some hours after the initial insult. We decided to test the hypothesis that membrane pump/ion channel activity or function is compromised and this would be reflected in structural changes within the axolemma and myelin sheath. We used freeze fracture and cytochemical techniques to provide evidence for change in membrane structure and the activity of membrane pumps after nondisruptive axonal injury in the adult guinea pig optic nerve. Within 10 min of injury, structural changes occurred in the distribution and number of intramembranous particles (IMPs) in the internodal axolemma. By 4 h, there was novel labeling for Ca-ATPase membrane pump activity at the same site. There was loss of IMPs from the nodal axolemma extending over several hours after injury. There was loss of both membrane pump Ca-ATPase and p-nitro-phenylphosphatase (p-NPPase) activity of the node. There was loss of ecto-Ca-ATPase activity but increased labeling for p-NPPase activity at sites of dissociation of compacted myelin. Quantitative freeze-fracture demonstrated statistically significant changes in membrane structure. We provide support for the hypothesis that structural and functional changes occur in the axolemma and myelin sheath at nondisruptive axonal injury.
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PMID:Freeze-fracture and cytochemical evidence for structural and functional alteration in the axolemma and myelin sheath of adult guinea pig optic nerve fibers after stretch injury. 1022 14

The protein kinase C (PKC) family of serine/threonine kinases functions downstream of nearly all membrane-associated signal transduction pathways. Here we identify PKC-alpha as a fundamental regulator of cardiac contractility and Ca(2+) handling in myocytes. Hearts of Prkca-deficient mice are hypercontractile, whereas those of transgenic mice overexpressing Prkca are hypocontractile. Adenoviral gene transfer of dominant-negative or wild-type PKC-alpha into cardiac myocytes enhances or reduces contractility, respectively. Mechanistically, modulation of PKC-alpha activity affects dephosphorylation of the sarcoplasmic reticulum Ca(2+) ATPase-2 (SERCA-2) pump inhibitory protein phospholamban (PLB), and alters sarcoplasmic reticulum Ca(2+) loading and the Ca(2+) transient. PKC-alpha directly phosphorylates protein phosphatase inhibitor-1 (I-1), altering the activity of protein phosphatase-1 (PP-1), which may account for the effects of PKC-alpha on PLB phosphorylation. Hypercontractility caused by Prkca deletion protects against heart failure induced by pressure overload, and against dilated cardiomyopathy induced by deleting the gene encoding muscle LIM protein (Csrp3). Deletion of Prkca also rescues cardiomyopathy associated with overexpression of PP-1. Thus, PKC-alpha functions as a nodal integrator of cardiac contractility by sensing intracellular Ca(2+) and signal transduction events, which can profoundly affect propensity toward heart failure.
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PMID:PKC-alpha regulates cardiac contractility and propensity toward heart failure. 1499 Oct 46

The most common microvascular diabetic complication, diabetic peripheral polyneuropathy (DPN), affects type 1 diabetic patients more often and more severely. In recent decades, it has become increasingly clear that perpetuating pathogenetic mechanisms, molecular, functional, and structural changes and ultimately the clinical expression of DPN differ between the two major types of diabetes. Impaired insulin/C-peptide action has emerged as a crucial factor to account for the disproportionate burden affecting type 1 patients. C-peptide was long believed to be biologically inactive. However, it has now been shown to have a number of insulin-like glucose-independent effects. Preclinical studies have demonstrated dose-dependent effects on Na+,K(+)-ATPase activity, endothelial nitric oxide synthase (eNOS), and endoneurial blood flow. Furthermore, it has regulatory effects on neurotrophic factors and molecules pivotal to the integrity of the nodal and paranodal apparatus and modulatory effects on apoptotic phenomena affecting the diabetic nervous system. In animal studies, C-peptide improves nerve conduction abnormalities, prevents nodal degenerative changes, characteristic of type 1 DPN, promotes nerve fiber regeneration, and prevents apoptosis of central and peripheral nerve cell constituents. Limited clinical trials have confirmed the beneficial effects of C-peptide on autonomic and somatic nerve function in patients with type 1 DPN. Therefore, evidence accumulates that replacement of C-peptide in type 1 diabetes prevents and even improves DPN. Large-scale food and drug administration (FDA)-approved clinical trials are necessary to make this natural substance available to the globally increasing type 1 diabetic population.
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PMID:Type 1 diabetic neuropathy and C-peptide. 1519 72

In Nicotiana plumbaginifolia, plasma membrane H(+)-ATPases (PMAs) are encoded by a gene family of nine members. Here, we report on the characterization of a new isogene, NpPMA5 (belonging to subfamily IV), and the determination of its expression pattern using the beta-glucuronidase (gusA) reporter gene. pNpPMA5-gusA was expressed in cotyledons, in vascular tissues of the stem (mainly in nodal zones), and in the flower and fruit. In the flower, high expression was found in the pollen tube after in vitro or in vivo germination. Northern blotting analysis confirmed that NpPMA5 was expressed in the pollen tube contrary to NpPMA2 (subfamily I) or NpPMA4 (subfamily II), two genes highly expressed in other tissues. The subcellular localization of PM H(+)-ATPase in the pollen tube was analyzed by immunocytodecoration. As expected, this enzyme was localized to the plasma membrane. However, neither the tip nor the base of the pollen tube was labeled, showing an asymmetrical distribution of this enzyme. This observation supports the hypothesis that the PM H(+)-ATPase is involved in creating the pH gradient that is observed along the pollen tube and is implicated in cell elongation. Compared to other plant PM H(+)-ATPases, the C-terminal region of NpPMA5 is shorter by 26 amino acid residues and is modified in the last 6 residues, due to a sequence rearrangement, which was also found in the orthologous gene of Nicotiana glutinosa, a Nicotiana species distant from N. plumbaginifolia and Petunia hybrida and Lycopersicon esculentum, other Solanacae species. This modification alters part of the PM H(+)-ATPase regulatory domain and raises the question whether this isoform is still regulated.
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PMID:Identification of a Nicotiana plumbaginifolia plasma membrane H(+)-ATPase gene expressed in the pollen tube. 1624 Jan 73

Vertebrate embryos develop distinct left-right asymmetry under the control of a conserved pathway involving left-sided deployment of the nodal and Pit x 2 genes. The mechanism that initiates asymmetric expression of these genes is less clear, with cilia, ion flux, and signalling molecules all implicated. Vertebrates share the chordate phylum with urochordates such as the sea squirt Ciona intestinalis. We have explored the role of ion flux in regulating left-right asymmetry in Ciona, using an assay in which perturbation of left-sided Ci-Pitx expression provides a read-out for the disruption of asymmetry. Our data show that omeprazole, which specifically inhibits H(+)K(+)ATPase activity, disrupts asymmetry in Ciona. The vertebrate H(+)K(+)ATPase is composed of two subunits, alpha and beta. We identified one Ciona beta ortholog and two Ciona alpha orthologs of the vertebrate H(+)K(+)ATPase genes, and show that one of these is expressed in dorsal and ventral embryonic midline cells shortly before the activation of left-sided Ci-Pitx expression. Furthermore, we show that omeprazole exerts its effect on asymmetry at this point in development, and additionally implicate K(+) channels in the regulation of asymmetry in Ciona. These experiments demonstrate a role for ion flux in the regulation of asymmetry in Ciona, and show a conserved, ancestral role for the H(+)K(+)ATPase ion pump in this process.
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PMID:Evidence for the regulation of left-right asymmetry in Ciona intestinalis by ion flux. 1658 45

P/Q-type calcium channels are known to form clusters at the presynaptic membrane where they mediate calcium influx, triggering vesicle fusion. We now report functional P/Q channel clusters in the axolemma of developing central axons that are also associated with sites of vesicle fusion. These channels were activated by axonal action potentials and the resulting calcium influx is well suited to mediate formation of a synaptic style SNARE complex involving SNAP-25, that we show to be located on the axolemma. Vesicular elements within axons were found to be the sole repository of vesicular glutamate in developing white matter. The axonal vesicular elements expressed the glutamate transporter V-ATPase, which is responsible for vesicular glutamate loading. The P/Q channel alpha(1A) subunit was found to be present within the axolemma at early nodes of Ranvier and deleterious mutations of the alpha(1A) subunit, or an associated alpha(2)delta-2 subunit, disrupted the localization of nodal proteins such as voltage-gated sodium channels, beta IV spectrin and CASPR-1. This was associated with the presence of malformed nodes of Ranvier characterized by an accumulation of axoplasmic vesicles under the nodal membrane. The data are consistent with the presence of a vesicular signalling pathway between axons and glial cells that is essential for proper development of the node of Ranvier.
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PMID:Vesicular apparatus, including functional calcium channels, are present in developing rodent optic nerve axons and are required for normal node of Ranvier formation. 1859 36

In mouse, the establishment of left-right (LR) asymmetry requires intracellular calcium (Ca(i)(2+)) enrichment on the left of the node. The use of Ca(i)(2+) asymmetry by other vertebrates, and its origins and relationship to other laterality effectors are largely unknown. Additionally, the architecture of Hensen's node raises doubts as to whether Ca(i)(2+) asymmetry is a broadly conserved mechanism to achieve laterality. We report here that the avian embryo uses a left-side enriched Ca(i)(2+) asymmetry across Hensen's node to govern its lateral identity. Elevated Ca(i)(2+) was first detected along the anterior node at early HH4, and its emergence and left-side enrichment by HH5 required both ryanodine receptor (RyR) activity and extracellular calcium, implicating calcium-induced calcium release (CICR) as the novel source of the Ca(i)(2+). Targeted manipulation of node Ca(i)(2+) randomized heart laterality and affected nodal expression. Bifurcation of the Ca(i)(2+) field by the emerging prechordal plate may permit the independent regulation of LR Ca(i)(2+) levels. To the left of the node, RyR/CICR and H(+)V-ATPase activity sustained elevated Ca(i)(2+). On the right, Ca(i)(2+) levels were actively repressed through the activities of H(+)K(+) ATPase and serotonin-dependent signaling, thus identifying a novel mechanism for the known effects of serotonin on laterality. Vitamin A-deficient quail have a high incidence of situs inversus hearts and had a reversed calcium asymmetry. Thus, Ca(i)(2+) asymmetry across the node represents a more broadly conserved mechanism for laterality among amniotes than had been previously believed.
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PMID:A ryanodine receptor-dependent Ca(i)(2+) asymmetry at Hensen's node mediates avian lateral identity. 1875 76

Diabetic polyneuropathy (DPN) is a common complication in diabetes. At present, there is no adequate treatment, and DPN is often debilitating for patients. It is a heterogeneous disorder and differs in type 1 and type 2 diabetes. An important underlying factor in type 1 DPN is insulin deficiency. Proinsulin C-peptide is a critical element in the cascade of events. In this review, we describe the physiological role of C-peptide and how it provides an insulin-like signaling function. Such effects translate into beneficial outcomes in early metabolic perturbations of neural Na+/K+-ATPase and nitric oxide (NO) with subsequent preventive effects on early nerve dysfunction. Further corrective consequences resulting from this signaling cascade have beneficial effects on gene regulation of early gene responses, neurotrophic factors, their receptors, and the insulin receptor itself. This may lead to preventive and corrective results to nerve fiber degeneration and loss, as well as, promotion of nerve fiber regeneration with respect to sensory somatic fibers and small nociceptive nerve fibers. A characteristic abnormality of type 1 DPN is nodal and paranodal degeneration with severe consequences for myelinated fiber function. This review deals in detail with the underlying insulin-deficiency-related molecular changes and their correction by C-peptide. Based on these observations, it is evident that continuous maintenance of insulin-like actions by C-peptide is needed in peripheral nerve to minimize the sequences of metabolic and molecular abnormalities, thereby ameliorating neuropathic complications. There is now ample evidence demonstrating that C-peptide replacement in type 1 diabetes promotes insulin action and signaling activities in a more enhanced, prolonged, and continuous fashion than does insulin alone. It is therefore necessary to replace C-peptide to physiological levels in diabetic patients. This will have substantial beneficial effects on type 1 DPN.
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PMID:The beneficial effects of C-Peptide on diabetic polyneuropathy. 2003 8


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