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- Synthesis and degradation of acetylcholine receptors in rat skeletal muscles were measured in organ culture. The rate of de novo biosynthesis and incorporation of acetylcholine receptors into extrajunctional membranes of denervated muscles was measured by determining the rate of appearance of [1] [2H, 13C, 15N]-acetylcholine receptors when muscles were cultured in medium containing [1] [2H, 13C, 15N]-amino acids. Denervated extensor digitorum longus and soleus muscles were found to synthesize new receptors for several days in organ culture at an average rate of 1.4%/h. The degradation rates for extrajunctional and junctional acetylcholine receptors were estimated by irreversibly labeling acétylcholine receptors on muscles with radioactive iodinated α-bungarotoxin and measuring the rate of release into the culture medium of mono- and di-iodotyrosine, breakdown products of the radioactive α-bungarotoxin. The rates of this proteolytic process yielded average lifetimes of 22 h and 13 days for [125I]α-bungarotoxin bound to extrajunctional and junctional receptors, respectively, probably reflecting the average lifetimes of the acetylcholine receptors. Electrical stimulation at 100Hz for 1 s every 80s, producing visible contraction, but not maximal tetanic tension, barely altered the rate of incorporation of new acetylcholine receptors into the extrajunctional plasma membrane of extensor digitorum longus and soleus muscles, even when the stimulation continued for 5 days. Supra-maximal stimulation, resulting in maximal tetanic tension, with the same stimulation pattern produced a rapid decline of 10–20% in the rate of new receptor production and a corresponding decline in overall protein synthesis. Stimulation beyond 18–24 h (up to 68 h) resulted in a further decrease in new receptor production to about 30% of the control rate, but not more. Stimulation for longer than 16 h produced less than a 5–10% decrease in overall protein synthesis, compared with control muscles. The same pattern of electrical stimulation, producing maximal tetanic tension, had no effect on the apparent degradation rate of extrajunctional receptors in denervated muscles. Our results show that denervated adult muscle can be maintained in organ culture for at least 1 week, and that the muscles in culture will continue to degrade acetylcholine receptors and to synthesize new receptors, even when electrically stimulated for 5 days. The significance of this study is that electrical stimulation, producing frequent tetanic contractions, can affect extrajunctional acetylcholine receptor metabolism by selectively decreasing de novo synthesis, the receptor degradation remaining unchanged. The precise control point in the biosynthetic process has yet to be determined. However, our results indicate that electrically induced activity does exert a regulating influence, relatively rapidly, on extrajunctional acetylcholine receptor metabolism on muscles maintained in vitro. (2)
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Articles 1 - 15 of 15
Full-Text Articles in Molecular and Cellular Neuroscience
Genetic And Acute Cpeb1 Depletion Ameliorate Fragile X Pathophysiology, Tsuyoshi Udagawa, Natalie Farny, Mira Jakovcevski, Hanoch Kaphzan, Juan Alarcon, Shobha Anilkumar, Maria Ivshina, Jessica Hurt, Kentaro Nagaoka, Vijayalaxmi Nalavadi, Lori Lorenz, Gary Bassell, Schahram Akbarian, Sumantra Chattarji, Eric Klann, Joel Richter
Genetic And Acute Cpeb1 Depletion Ameliorate Fragile X Pathophysiology, Tsuyoshi Udagawa, Natalie Farny, Mira Jakovcevski, Hanoch Kaphzan, Juan Alarcon, Shobha Anilkumar, Maria Ivshina, Jessica Hurt, Kentaro Nagaoka, Vijayalaxmi Nalavadi, Lori Lorenz, Gary Bassell, Schahram Akbarian, Sumantra Chattarji, Eric Klann, Joel Richter
Natalie G. Farny
Fragile X syndrome (FXS), the most common cause of inherited mental retardation and autism, is caused by transcriptional silencing of FMR1, which encodes the translational repressor fragile X mental retardation protein (FMRP). FMRP and cytoplasmic polyadenylation element-binding protein (CPEB), an activator of translation, are present in neuronal dendrites, are predicted to bind many of the same mRNAs and may mediate a translational homeostasis that, when imbalanced, results in FXS. Consistent with this possibility, Fmr1(-/y); Cpeb1(-/-) double-knockout mice displayed amelioration of biochemical, morphological, electrophysiological and behavioral phenotypes associated with FXS. Acute depletion of CPEB1 in the hippocampus of adult Fmr1(-/y) mice …
Comparison Between Coated Vs. Uncoated Suture Middle Cerebral Artery Occlusion In The Rat As Assessed By Perfusion/Diffusion Weighted Imaging, James Bouley, Marc Fisher, Nils Henninger
Comparison Between Coated Vs. Uncoated Suture Middle Cerebral Artery Occlusion In The Rat As Assessed By Perfusion/Diffusion Weighted Imaging, James Bouley, Marc Fisher, Nils Henninger
Nils Henninger
Differences among models in the temporal evolution of ischemia after middle cerebral artery occlusion (MCAO) in rats may considerably influence the results of experimental treatment studies. Using diffusion and perfusion imaging, we compared the spatiotemporal evolution of ischemia in Sprague-Dawley rats after permanent MCAO (pMCAO) with different types of sutures. Male Sprague-Dawley rats were randomly assigned to pMCAO produced with either 4-0 silicone coated (n=8), or 3-0 uncoated monofilaments (n=8). Serial determination of quantitative cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) maps were performed up to 3 h after pMCAO. Lesion volumes were calculated by using previously validated …
Polychlorinated Biphenyl Exposure Alters Oxytocin Receptor Gene Expression And Maternal Behavior In Rat, Howard Cromwell
Polychlorinated Biphenyl Exposure Alters Oxytocin Receptor Gene Expression And Maternal Behavior In Rat, Howard Cromwell
Howard Casey Cromwell
Polychlorinated biphenyl (PCB) is a persistent organic pollutant known to induce diverse molecular and behavioral alterations. Effects of PCB exposure could be transmitted to future generations via changes in behavior and gene expression. Previous work has shown that PCB-exposure can alter social behavior. The present study extends this work by examining a possible molecular mechanism for these changes. Pregnant rats (Sprague-Dawley) were exposed through diet to a combination of non-coplanar (PCB 47 - 2,20,4,40-tetrachlorobiphenyl) and coplanar (PCB 77 - 3,30,4,40- tetrachlorobiphenyl) congeners. Maternal care behaviors were examined by evaluating the rate and quality of nest building on the last 4 …
Controlling Feeding Behavior By Chemical Or Gene-Directed Targeting In The Brain: What’S So Spatial About Our Methods?, Arshad Khan
Arshad M. Khan, Ph.D.
Intracranial chemical injection (ICI) methods have been used to identify the locations in the brain where feeding behavior can be controlled acutely. Scientists conducting ICI studies often document their injection site locations, thereby leaving kernels of valuable location data for others to use to further characterize feeding control circuits. Unfortunately, this rich dataset has not yet been formally contextualized with other published neuroanatomical data. In particular, axonal tracing studies have delineated several neural circuits originating in the same areas where ICI injection feeding-control sites have been documented, but it remains unclear whether these circuits participate in feeding control. However, comparing …
Alcohol-Induced Il-1beta In The Brain Is Mediated By Nlrp3/Asc Inflammasome Activation That Amplifies Neuroinflammation, Dora Lippai, Shashi Bala, Jan Petrasek, Timea Csak, Ivan Levin, Evelyn Kurt-Jones, Gyongyi Szabo
Alcohol-Induced Il-1beta In The Brain Is Mediated By Nlrp3/Asc Inflammasome Activation That Amplifies Neuroinflammation, Dora Lippai, Shashi Bala, Jan Petrasek, Timea Csak, Ivan Levin, Evelyn Kurt-Jones, Gyongyi Szabo
Gyongyi Szabo
Alcohol-induced neuroinflammation is mediated by proinflammatory cytokines, including IL-1beta. IL-1beta production requires caspase-1 activation by inflammasomes-multiprotein complexes that are assembled in response to danger signals. We hypothesized that alcohol-induced inflammasome activation contributes to increased IL-1beta in the brain. WT and TLR4-, NLRP3-, and ASC-deficient (KO) mice received an ethanol-containing or isocaloric control diet for 5 weeks, and some received the rIL-1ra, anakinra, or saline treatment. Inflammasome activation, proinflammatory cytokines, endotoxin, and HMGB1 were measured in the cerebellum. Expression of inflammasome components (NLRP1, NLRP3, ASC) and proinflammatory cytokines (TNF-alpha, MCP-1) was increased in brains of alcohol-fed compared with control mice. Increased …
Dopamine Transporter Endocytic Trafficking In Striatal Dopaminergic Neurons: Differential Dependence On Dynamin And The Actin Cytoskeleton., Haley Melikian
Dopamine Transporter Endocytic Trafficking In Striatal Dopaminergic Neurons: Differential Dependence On Dynamin And The Actin Cytoskeleton., Haley Melikian
Haley Melikian
Dopaminergic signaling profoundly impacts rewarding behaviors, movement, and executive function. The presynaptic dopamine (DA) transporter (DAT) recaptures released DA, thereby limiting synaptic DA availability and maintaining dopaminergic tone. DAT constitutively internalizes and PKC activation rapidly accelerates DAT endocytosis, resulting in DAT surface loss. Longstanding evidence supports PKC-stimulated DAT trafficking in heterologous expression studies. However, PKC-stimulated DAT internalization is not readily observed in cultured dopaminergic neurons. Moreover, conflicting reports implicate both classic and nonclassic endocytic mechanisms mediating DAT trafficking. Prior DAT trafficking studies relied primarily upon chronic gene disruption and dominant-negative protein expression, or were performed in cell lines and cultured …
Pleiotropic And Isoform-Specific Functions For Pitx2 In Superior Colliculus And Hypothalamic Neuronal Development, Mindy Waite
Pleiotropic And Isoform-Specific Functions For Pitx2 In Superior Colliculus And Hypothalamic Neuronal Development, Mindy Waite
Mindy Waite
A Novel Taulacz Allele Reveals A Requirement For Pitx2 In Formation Of The Mammillothalamic Tract, Mindy Waite
A Novel Taulacz Allele Reveals A Requirement For Pitx2 In Formation Of The Mammillothalamic Tract, Mindy Waite
Mindy Waite
Distinct Populations Of Gabaergic Neurons In Mouse Rhombomere 1 Express But Do Not Require The Homeodomain Transcription Factor Pitx2, Mindy Waite
Mindy Waite
Gabaergic And Glutamatergic Identities Of Developing Midbrain Pitx2 Neurons, Mindy Waite
Gabaergic And Glutamatergic Identities Of Developing Midbrain Pitx2 Neurons, Mindy Waite
Mindy Waite
Nonclassical, Distinct Endocytic Signals Dictate Constitutive And Pkc-Regulated Neurotransmitter Transporter Internalization, Haley Melikian
Nonclassical, Distinct Endocytic Signals Dictate Constitutive And Pkc-Regulated Neurotransmitter Transporter Internalization, Haley Melikian
Haley Melikian
Neurotransmitter transporters are critical for synaptic neurotransmitter inactivation. Transporter inhibitors markedly increase the duration and magnitude of synaptic transmission, underscoring the importance of transporter activity in neurotransmission. Recent studies indicate that membrane trafficking dynamically governs neuronal transporter cell-surface presentation in a protein kinase C-regulated manner, suggesting that transporter trafficking profoundly affects synaptic signaling. However, the molecular architecture coupling neurotransmitter transporters to the endocytic machinery is not defined. Here, we identify nonclassical, distinct endocytic signals in the dopamine transporter (DAT) that are necessary and sufficient to drive constitutive and protein kinase C-regulated DAT internalization. The DAT internalization signal is conserved across …
Neuromuscular Junction Development In The Cutaneous Pectoris Muscle Of Rana Catesbeiana, Diana Linden, Susan Jerian, Michael Letinsky
Neuromuscular Junction Development In The Cutaneous Pectoris Muscle Of Rana Catesbeiana, Diana Linden, Susan Jerian, Michael Letinsky
Diana Linden
Synaptic specializations were studied in the developing cutaneous pectoris muscle of Rana catesbeiana tadpoles and froglets to correlate nerve terminal morphology (by light and electron microscopy), accumulation of acetylcholine receptors, and the ability of the muscle to contract following nerve stimulation. This correlated approach was used to determine the developmental timing and possible causal relationship of events in nerve and muscle maturation at the neuromuscular junction. Initially, the cutaneous pectoris nerve trunk was present in the undifferentiated presumptive cutaneous pectoris mesenchyme, prior to muscle maturation. At stage XII when the muscle was first able to contract weakly in response to …
Correlated Muscle And Nerve Development In The Bullfrog Cutaneous Pectoris, Diana Linden, Michael Letinsky
Correlated Muscle And Nerve Development In The Bullfrog Cutaneous Pectoris, Diana Linden, Michael Letinsky
Diana Linden
The development of the cutaneous pectoris muscle was studied and compared with the differentiation of its peripheral nerve in bullfrog (Rana catesbeiana) tadpoles and frogs by light and electron microscopic techniques. This muscle preparation was chosen for this study because it possesses a number of advantages for (and has become a model system for) the study of correlated nerve-muscle development. At the earliest stage examined (stage XI) the presumptive muscle did not contain any contractile or morphologically distinguishable myotubes, but was contacted by the well-defined cutaneous pectoris nerve trunk. Myotubes were present at stage XII, the same time that nerve-associated …
Rapid Decline In Acetylcholine Release And Content Of Rat Extensor Digitorum Longus Muscle After Denervation, Diana Linden, Michael Newton, Alan Grinnell, Donald Jenden
Rapid Decline In Acetylcholine Release And Content Of Rat Extensor Digitorum Longus Muscle After Denervation, Diana Linden, Michael Newton, Alan Grinnell, Donald Jenden
Diana Linden
The amount of acetylcholine (ACh) and choline (Ch) in normal and denervated rat extensor digitorum longus (EDL) muscles, as well as that released spontaneously from these muscles, was determined by an extremely sensitive gas chromatographicmass spectrometric assay method. We found decreases in ACh content and spontaneous, resting ACh release as early as 8 h after denervation. The ACh content decreased to a plateau of 30% of control by 11 h; ACh release attained a plateau of 50% of control several hours later. These results showed that in denervated EDL muscles ACh content and spontaneous release (measured biochemically) decreased before nerve-evoked …
Biosynthesis And Degradation Of Acetylcholine Receptors In Rat Skeletal Muscles. Effects Of Electrical Stimulation, Diana Linden, D.M. Fambrough
Biosynthesis And Degradation Of Acetylcholine Receptors In Rat Skeletal Muscles. Effects Of Electrical Stimulation, Diana Linden, D.M. Fambrough
Diana Linden
Synthesis and degradation of acetylcholine receptors in rat skeletal muscles were measured in organ culture. The rate of de novo biosynthesis and incorporation of acetylcholine receptors into extrajunctional membranes of denervated muscles was measured by determining the rate of appearance of [1] [2H, 13C, 15N]-acetylcholine receptors when muscles were cultured in medium containing [1] [2H, 13C, 15N]-amino acids. Denervated extensor digitorum longus and soleus muscles were found to synthesize new receptors for several days in organ culture at an average rate of 1.4%/h. The degradation rates for extrajunctional and junctional acetylcholine receptors were estimated by irreversibly labeling acétylcholine receptors on …