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Neuronal Membrane (neuronal + membrane)
Selected AbstractsDo neurons have a reserve of sodium channels for the generation of action potentials?EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2000A study on acutely isolated CA1 neurons from the guinea-pig hippocampus Abstract The density of voltage-gated sodium channels is high in several regions of the neuronal membrane. It is unclear if this density of channels represents a reserve for the neuron, or if it fulfils a special role in action potential firing. This problem was addressed by studying sodium currents and action potentials in acutely isolated hippocampal CA1 neurons whose number of active sodium channels was acutely changed by applying the sodium channel blocker tetrodotoxin (TTX) at different concentrations. The results show that more than a third of the sodium channels can fail without affecting the single action potential. Thus, the neurons have a remarkable surplus of sodium channels. The surplus, however, is necessary for repetitive action potential firing, as every decrease in the fraction of sodium channels reduces the maximal frequency of action potentials that can be generated by the neuron. [source] Increased turnover of Na-K ATPase molecules in rat brain after rapid eye movement sleep deprivationJOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2003Sudipta Majumdar Abstract It has been shown that rapid eye movement (REM) sleep deprivation increases Na-K ATPase activity. Based on kinetic study, it was proposed that increased activity was due to enhanced turnover of enzyme molecules. To test this, anti-,1 Na-K ATPase monoclonal antibody (mAb 9A7) was used to label Na-K ATPase molecules. These labeled enzymes were quantified on neuronal membrane by two methods: histochemically on neurons in tissue sections from different brain areas, and by Western blot analysis in control and REM sleep-deprived rat brains. The specific enzyme activity was also estimated and found to be increased, as in previous studies. The results confirmed our hypothesis that after REM sleep deprivation, increased Na-K ATPase activity was at least partly due to increased turnover of Na-K ATPase molecules in the rat brain. © 2003 Wiley-Liss, Inc. [source] Interaction of a ,-sheet breaker peptide with lipid membranesJOURNAL OF PEPTIDE SCIENCE, Issue 2 2010Giuseppe Vitiello Abstract Aggregation of ,-amyloid peptides into senile plaques has been identified as one of the hallmarks of Alzheimer's disease. An attractive therapeutic strategy for Alzheimer's disease is the inhibition of the soluble ,-amyloid aggregation using synthetic ,-sheet breaker peptides that are capable of binding A, but are unable to become part of a ,-sheet structure. As the early stages of the A, aggregation process are supposed to occur close to the neuronal membrane, it is strategic to define the ,-sheet breaker peptide positioning with respect to lipid bilayers. In this work, we have focused on the interaction between the ,-sheet breaker peptide acetyl-LPFFD-amide, iA,5p, and lipid membranes, studied by ESR spectroscopy, using either peptides alternatively labeled at the C- and at the N-terminus or phospholipids spin-labeled in different positions of the acyl chain. Our results show that iA,5p interacts directly with membranes formed by the zwitterionic phospholipid dioleoyl phosphatidylcholine and this interaction is modulated by inclusion of cholesterol in the lipid bilayer formulation, in terms of both peptide partition coefficient and the solubilization site. In particular, cholesterol decreases the peptide partition coefficient between the membrane and the aqueous medium. Moreover, in the absence of cholesterol, iA,5p is located between the outer part of the hydrophobic core and the external hydrophilic layer of the membrane, while in the presence of cholesterol it penetrates more deeply into the lipid bilayer. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd. [source] 5-Hydroxytryptamine selectively activates the vagal nodose C-fibre subtype in the guinea-pig oesophagusNEUROGASTROENTEROLOGY & MOTILITY, Issue 9 2008S. Yu Abstract, The afferent neurons innervating the oesophagus originate from two embryonic sources: neurons located in vagal nodose ganglia originate from embryonic placodes and neurons located in vagal jugular and spinal dorsal root ganglia (DRG) originate from the neural crest. Here, we address the hypothesis that 5-hydroxytryptamine (5-HT) differentially stimulates afferent nerve subtypes in the oesophagus. Extracellular recordings of single unit activity originating from nerve terminals were made in the isolated innervated guinea-pig oesophagus. Whole cell patch clamp recordings (35 °C) were made from the primary afferent neurons retrogradely labelled from the oesophagus. 5-Hydroxytryptamine (10 ,mol L,1) activated vagal nodose C-fibres (70%) in the oesophagus but failed to activate overtly vagal jugular nerve fibres and oesophagus-specific spinal DRG neurons. The response to 5-HT in nodose C-fibre nerve terminals was mimicked by the selective 5-HT3 receptor agonist 2-methyl-5-HT (10 ,mol L,1) and nearly abolished by the 5-HT3 receptor antagonists ondansetron (10 ,mol L,1) and Y-25130 (10 ,mol L,1). In patch clamp studies, 2-methyl-5-HT (10 ,mol L,1) activated a proportion of isolated oesophagus-specific nodose capsaicin-sensitive neurons (putative cell bodies of nodose C-fibres). We conclude that the responsiveness to 5-HT discriminates placode-derived (vagal nodose) C-fibres from the neural crest-derived (vagal jugular and spinal DRG) afferent nerves in the oesophagus. The response to 5-HT in nodose C-fibres is mediated by the 5-HT3 receptor in their neuronal membrane. [source] Lipid-induced conformational transition of the amyloid core fragment A,(28,35) and its A30G and A30I mutantsFEBS JOURNAL, Issue 10 2008Sureshbabu Nagarajan The interaction of the ,-amyloid peptide (A,) with neuronal membranes could play a key role in the pathogenesis of Alzheimer's disease. Recent studies have focused on the interactions of A, oligomers to explain the neuronal toxicity accompanying Alzheimer's disease. In our study, we have investigated the role of lipid interactions with soluble A,(28,35) (wild-type) and its mutants A30G and A30I in their aggregation and conformational preferences. CD and Trp fluorescence spectroscopic studies indicated that, immediately on dissolution, these peptides adopted a random coil structure. Upon addition of negatively charged 1,2-dipalmitoyl- syn -glycero-3-phospho- rac -(glycerol) sodium salt (PG) lipid, the wild-type and A30I mutant underwent reorganization into a predominant ,-sheet structure. However, no conformational changes were observed in the A30G mutant on interaction with PG. In contrast, the presence of zwitterionic 1,2-dipalmitoyl- syn -glycero-3-phosphatidylcholine (PC) lipid had no effect on the conformation of these three peptides. These observations were also confirmed with atomic force microscopy and the thioflavin-T assay. In the presence of PG vesicles, both the wild-type and A30I mutant formed fibrillar structures within 2 days of incubation in NaCl/Pi, but not in their absence. Again, no oligomerization was observed with PC vesicles. The Trp studies also revealed that both ends of the three peptides are not buried deep in the vesicle membrane. Furthermore, fluorescence spectroscopy using the environment-sensitive probe 1,6-diphenyl-1,3,5-hexatriene showed an increase in the membrane fluidity upon exposure of the vesicles to the peptides. The latter effect may result from the lipid head group interactions with the peptides. Fluorescence resonance energy transfer experiments revealed that these peptides undergo a random coil-to-sheet conversion in solution on aging and that this process is accelerated by negatively charged lipid vesicles. These results indicate that aggregation depends on hydrophobicity and propensity to form ,-sheets of the amyloid peptide, and thus offer new insights into the mechanism of amyloid neurodegenerative disease. [source] Trisialoganglioside GT1b induces in vivo degeneration of nigral dopaminergic neurons: Role of microgliaGLIA, Issue 1 2002Jae K. Ryu Abstract We recently showed that trisialoganglioside (GT1b) induces cell death of dopaminergic neurons in rat mesencephalic cultures (Chung et al., Neuroreport 12:611,614, 2001). The present study examines the in vivo neurotoxic effects of GT1b on dopaminergic neurons in the substantia nigra (SN) of Sprague-Dawley rats. Seven days after GT1b injection into the SN, immunocytochemical staining of SN tissue revealed death of nigral neurons, including dopaminergic neurons. Additional immunostaining using OX-42 and OX-6 antibodies showed that GT1b-activated microglia were present in the SN where degeneration of nigral neurons was found. Western blot analysis and double-labeled immunohistochemistry showed that inducible nitric oxide synthase (iNOS) was expressed in the SN, where its levels were maximal at 8 h post-GT1b injection, and that iNOS was localized exclusively within microglia. GT1b-induced loss of dopaminergic neurons in the SN was partially inhibited by NG -nitro-L-arginine methyl ester hydrochloride, an NOS inhibitor. Our results indicate that in vivo neurotoxicity of GT1b against nigral dopaminergic neurons is at least in part mediated by nitric oxide released from activated microglia. Because GT1b exists abundantly in central nervous system neuronal membranes, our data support the hypothesis that immune-mediated events triggered by endogenous compounds such as GT1b could contribute to the initiation and/or the progression of dopaminergic neuronal cell death that occurs in Parkinson's disease. GLIA 38:15,23, 2002. © 2002 Wiley-Liss, Inc. [source] Imbalance of plasma membrane ion leak and pump relationship as a new aetiological basis of certain disease statesJOURNAL OF INTERNAL MEDICINE, Issue 6 2003G. Ronquist Abstract. The basis for life is the ability of the cell to maintain ion gradients across biological membranes. Such gradients are created by specific membrane-bound ion pumps [adenosine triphosphatases (ATPases)]. According to physicochemical rules passive forces equilibrate (dissipate) ion gradients. The cholesterol/phospholipid ratio of the membrane and the degree of saturation of phospholipid fatty acids are important factors for membrane molecular order and herewith a determinant of the degree of non-specific membrane leakiness. Other operative principles, i.e. specific ion channels can be opened and closed according to mechanisms that are specific to the cell. Certain compounds called ionophores can be integrated in the plasma membrane and permit specific inorganic ions to pass. Irrespective of which mechanism ions leak across the plasma membrane the homeostasis may be kept by increasing ion pumping (ATPase activity) in an attempt to restore the physiological ion gradient. The energy source for this work seems to be glycolytically derived ATP formation. Thus an increase in ion pumping is reflected by increased ATP hydrolysis and rate of glycolysis. This can be measured as an accumulation of breakdown products of ATP and end-products of anaerobic glycolysis (lactate). In certain disease entities, the balance between ATP formation and ion pumping may be disordered resulting in a decrease in inter alia (i.a.) cellular energy charge, and an increase in lactate formation and catabolites of adenylates. Cardiac syndrome X is proposed to be due to an excessive leakage of potassium ions, leading to electrocardiographic (ECG) changes, abnormal Tl-scintigraphy of the heart and anginal pain (induced by adenosine). Cocksackie B3 infections, a common agent in myocarditis might also induce an ionophore-like effect. Moreover, Alzheimer's disease is characterized by the formation of extracellular amyloid deposits in the brain of patients. Perturbation of cellular membranes by the amyloid peptide during the development of Alzheimer's disease is one of several mechanisms proposed to account for the toxicity of this peptide on neuronal membranes. We have studied the effects of the peptide and fragments thereof on 45Ca2+ -uptake in human erythrocytes and the energetic consequences. Treatment of erythrocytes with the ,1,40 peptide, results in qualitatively similar nucleotide pattern and decrease of energy charge as the treatment with Ca2+ -ionophore A23187. Finally, in recent studies we have revealed and published in this journal that a rare condition, Tarui's disease or glycogenosis type VII, primarily associated with a defect M-subunit of phosphofructokinase, demonstrates as a cophenomenon an increased leak of Ca2+ into erythrocytes. [source] | ||||||||||||||||