scholarly journals Cl− concentration changes and desensitization of GABAA and glycine receptors

2011 ◽  
Vol 138 (6) ◽  
pp. 609-626 ◽  
Author(s):  
Urban Karlsson ◽  
Michael Druzin ◽  
Staffan Johansson
Keyword(s):  
Information Transfer ◽  
Critical Role ◽  
Minor Role ◽  
Current View ◽  
Glycine Receptors ◽  
Gaba A ◽  
Current Decay ◽  
Central Neurons ◽  
Concentration Changes ◽  
A Minor

Desensitization of ligand-gated ion channels plays a critical role for the information transfer between neurons. The current view on γ-aminobutyric acid (GABA)A and glycine receptors includes significant rapid components of desensitization as well as cross-desensitization between the two receptor types. Here, we analyze the mechanism of apparent cross-desensitization between native GABAA and glycine receptors in rat central neurons and quantify to what extent the current decay in the presence of ligand is a result of desensitization versus changes in intracellular Cl− concentration ([Cl−]i). We show that apparent cross-desensitization of currents evoked by GABA and by glycine is caused by changes in [Cl−]i. We also show that changes in [Cl−]i are critical for the decay of current in the presence of either GABA or glycine, whereas changes in conductance often play a minor role only. Thus, the currents decayed significantly quicker than the conductances, which decayed with time constants of several seconds and in some cells did not decay below the value at peak current during 20-s agonist application. By taking the cytosolic volume into account and numerically computing the membrane currents and expected changes in [Cl−]i, we provide a theoretical framework for the observed effects. Modeling diffusional exchange of Cl− between cytosol and patch pipettes, we also show that considerable changes in [Cl−]i may be expected and cause rapidly decaying current components in conventional whole cell or outside-out patch recordings. The findings imply that a reevaluation of the desensitization properties of GABAA and glycine receptors is needed.

Excitatory Actions of Vasoactive Intestinal Peptide on Mouse Thalamocortical Neurons Are Mediated by VPAC2 Receptors

2006 ◽  
Vol 96 (2) ◽  
pp. 858-871 ◽  
Author(s):  
Sang-Hun Lee ◽  
Charles L. Cox
Keyword(s):  
Vasoactive Intestinal Peptide ◽  
Information Transfer ◽  
Receptor Activation ◽  
Absence Epilepsy ◽  
Minor Role ◽  
Receptor Subtype ◽  
Thalamic Nuclei ◽  
Knock Out ◽  
A Minor ◽  
Relay Neurons

Thalamic nuclei can generate intrathalamic rhythms similar to those observed at various arousal levels and pathophysiological conditions such as absence epilepsy. These rhythmic activities can be altered by a variety of neuromodulators that arise from brain stem regions as well as those that are intrinsic to the thalamic circuitry. Vasoactive intestinal peptide (VIP) is a neuropeptide localized within the thalamus and strongly attenuates intrathalamic rhythms via an unidentified receptor subtype. We have used transgenic mice lacking a specific VIP receptor, VPAC2, to identify its role in VIP-mediated actions in the thalamus. VIP strongly attenuated both the slow, 2–4 Hz and spindle-like 5–8 Hz rhythmic activities in slices from wild-type mice (VPAC2+/+) but not in slices from VPAC2 receptor knock-out mice (VPAC2−/−), which suggests a major role of VPAC2 receptors in the antioscillatory actions of VIP. Intracellular recordings revealed that VIP depolarized all relay neurons tested from VPAC2+/+ mice. In VPAC2−/− mice, however, VIP produced no membrane depolarization in 80% of neurons tested. In relay neurons from VPAC2+/+ mice, VIP enhanced the hyperpolarization-activated mixed cation current, Ih, via cyclic AMP activity, but VIP did not alter Ih in VPAC2−/− mice. In VPAC2−/− mice, pituitary adenylate cyclase activating-polypeptide (PACAP) depolarized the majority of relay neurons via Ih enhancement presumably via PAC1 receptor activation. Our findings suggest that VIP-mediated actions are predominantly mediated by VPAC2 receptors, but PAC1 receptors may play a minor role. The excitatory actions of VIP and PACAP suggest these peptides may not only regulate intrathalamic rhythmic activities, but also may influence information transfer through thalamocortical circuits.

scholarly journals The Phage T4 Antiholin RI Has a Cleavable Signal Peptide, Not a SAR Domain

2021 ◽  
Vol 12 ◽  
Author(s):  
Denise Mehner-Breitfeld ◽  
Jan Michel Frederik Schwarzkopf ◽  
Ry Young ◽  
Kiran Kondabagil ◽  
Thomas Brüser
Keyword(s):  
Signal Peptide ◽  
Current Model ◽  
Signal Peptidase ◽  
Minor Role ◽  
Current View ◽  
T Complex ◽  
Phage T4 ◽  
Membrane Lysis ◽  
Signal Anchor ◽  
A Minor

Holin/endolysin-mediated lysis of phage T4 of Escherichia coli is tightly regulated by the antiholins RI and RIII. While regulation by the cytoplasmic RIII plays a minor role, the periplasmic antiholin RI binds tightly to the holin T and is believed to directly sense periplasmic phage DNA from superinfections as a trigger for the inhibition of lysis. RI has been reported to contain a non-cleavable signal peptide that anchors the protein to the membrane. Lysis is believed to be induced at some stage by a membrane depolarization that causes a release of RI into the periplasm without cleavage of the signal anchor. For the current model of phage lysis induction, it is thus a fundamental assumption that the N-terminal trans-membrane domain (TMD) of RI is such a signal anchor release (SAR) domain. Here we show that, in contrast to previous reports, this domain of RI is a cleavable signal peptide. RI is processed and released into the periplasm as a mature protein, and inactivation of its signal peptidase cleavage site blocks processing and membrane release. The signal peptide of RI can also mediate the normal translocation of a well-characterized Sec substrate, PhoA, into the periplasm. This simplifies the current view of phage lysis regulation and suggests a fundamentally different interpretation of the recently published structure of the soluble domains of the RI–T complex.

scholarly journals Loss of CCR5 results in glucose intolerance in diet-induced obese mice

2013 ◽  
Vol 305 (7) ◽  
pp. E897-E906 ◽  
Author(s):  
Arion Kennedy ◽  
Corey D. Webb ◽  
Andrea A. Hill ◽  
Marnie L. Gruen ◽  
Laurel G. Jackson ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Cell ◽  
Critical Role ◽  
Cell Infiltration ◽  
Minor Role ◽  
Immune Cell Infiltration ◽  
T Cell Infiltration ◽  
Mild Reduction ◽  
Plasma Insulin Levels ◽  
A Minor

Macrophage and T cell infiltration into metabolic tissues contributes to obesity-associated inflammation and insulin resistance (IR). C-C chemokine receptor 5 (CCR5), expressed on macrophages and T cells, plays a critical role in the recruitment and activation of proinflammatory M1 and TH1 immune cells to tissues and is elevated in adipose tissue (AT) and liver of obese humans and mice. Thus, we hypothesized that deficiency of CCR5 would protect against diet-induced inflammation and IR. CCR5-deficient (CCR5−/−) mice and C57BL/6 (WT) controls were fed 10% low-fat (LF) or 60% high-fat (HF) diets for 16 wk. HF feeding increased adiposity, blood glucose, and plasma insulin levels equally in both genotypes. Opposing our hypothesis, HF-fed CCR5−/− mice were significantly more glucose intolerant than WT mice. In AT, there was a significant reduction in the M1-associated gene CD11c, whereas M2 associated genes were not different between genotypes. In addition, HF feeding caused a twofold increase in CD4+ T cells in the AT of CCR5−/− compared with WT mice. In liver and muscle, no differences in immune cell infiltration or inflammatory cytokine expression were detected. However, in AT and muscle, there was a mild reduction in insulin-induced phosphorylation of AKT and IRβ in CCR5−/− compared with WT mice. These findings suggest that whereas CCR5 plays a minor role in regulating immune cell infiltration and inflammation in metabolic tissues, deficiency of CCR5 impairs systemic glucose tolerance as well as AT and muscle insulin signaling.

An invited article: Phonological recoding and reading acquisition

1983 ◽  
Vol 4 (2) ◽  
pp. 103-147 ◽  
Author(s):  
Anthony F. Jorm ◽  
David L. Share
Keyword(s):  
Phonological Processing ◽  
Word Identification ◽  
Critical Role ◽  
Minor Role ◽  
Phonological Recoding ◽  
Adult Reading ◽  
A Minor ◽  
Developmental Analysis ◽  
Teaching Implications

ABSTRACTPhonological recoding is commonly viewed as a back-up mechanism when word identification using the visual pathway fails. A second more important role for phonological recoding is as a self-teaching mechanism by which the child learns to identify words visually. Although phonological recoding may play a minor role in skilled adult reading, it plays a critical role in helping the child become a skilled reader. This article reviews the evidence relevant to these issues. The first section examines evidence on the role of phonological recoding in the development of word identification skills and reading comprehension. The next section reviews evidence showing that children with reading disabilities often have deficits in basic phonological processing skills. The third section deals with the nature of the reading problem in such children which, it is argued, is consistent with the proposed developmental analysis of the importance of phonological recoding in learning to read. The article concludes with a discussion of the teaching implications of these conclusions.

scholarly journals Mdm38 interacts with ribosomes and is a component of the mitochondrial protein export machinery

2006 ◽  
Vol 172 (4) ◽  
pp. 553-564 ◽  
Author(s):  
Ann E. Frazier ◽  
Rebecca D. Taylor ◽  
David U. Mick ◽  
Bettina Warscheid ◽  
Nadine Stoepel ◽  
...  
Keyword(s):  
Respiratory Chain ◽  
Protein Transport ◽  
Critical Role ◽  
Mitochondrial Protein ◽  
Complex Iii ◽  
Minor Role ◽  
Central Component ◽  
Inner Membrane ◽  
Mitochondrial Ribosomes ◽  
A Minor

Saccharomyces cerevisiae Mdm38 and Ylh47 are homologues of human Letm1, a protein implicated in Wolf-Hirschhorn syndrome. We analyzed the function of Mdm38 and Ylh47 in yeast mitochondria to gain insight into the role of Letm1. We find that mdm38Δ mitochondria have reduced amounts of certain mitochondrially encoded proteins and low levels of complex III and IV and accumulate unassembled Atp6 of complex V of the respiratory chain. Mdm38 is especially required for efficient transport of Atp6 and cytochrome b across the inner membrane, whereas Ylh47 plays a minor role in this process. Both Mdm38 and Ylh47 form stable complexes with mitochondrial ribosomes, similar to what has been reported for Oxa1, a central component of the mitochondrial export machinery. Our results indicate that Mdm38 functions as a component of an Oxa1-independent insertion machinery in the inner membrane and that Mdm38 plays a critical role in the biogenesis of the respiratory chain by coupling ribosome function to protein transport across the inner membrane.

scholarly journals Gene expression during inactivity-induced muscle atrophy: effects of brief bouts of a forceful contraction countermeasure

2008 ◽  
Vol 105 (4) ◽  
pp. 1246-1254 ◽  
Author(s):  
Soo J. Kim ◽  
Roland R. Roy ◽  
Jung A. Kim ◽  
Hui Zhong ◽  
Fadia Haddad ◽  
...  
Keyword(s):  
High Resistance ◽  
Muscle Protein ◽  
Critical Role ◽  
Ring Finger ◽  
Specific Protein ◽  
Medial Gastrocnemius ◽  
Minor Role ◽  
Isometric Contractions ◽  
Adult Rats ◽  
A Minor

Anabolic and catabolic markers of muscle protein metabolism were examined in inactivity-induced atrophying muscles with and without daily short-duration, high-resistance isometric contractions. Inactivity was achieved via spinal cord isolation (SI), which results in near inactivity of the hindlimb musculature without compromising the motoneuron-muscle connectivity. Adult rats were assigned to a control (Con) or SI group in which one limb was stimulated (SI-Stim, 5 consecutive days of brief bouts of high-load isometric contractions) while the other served as a SI control (SI). Both the medial gastrocnemius (MG) and soleus weights (relative to body weight) were ∼71% of Con in the SI, but maintained at Con in the SI-Stim group. Activity of the IGF-1/phosphatidylinositol 3-kinase (PI3K)/Akt pathway of protein synthesis was similar among all groups in the MG. Expression of atrogin-1 and muscle RING finger-1 (MuRF-1), markers of protein degradation, were higher in the MG and soleus of the SI than Con and maintained at Con in the SI-Stim. Compared with Con, the anti-growth factor myostatin was unaffected in the MG and soleus in the SI but was lower in the MG of the SI-Stim. These results demonstrate that upregulation of specific protein catabolic pathways plays a critical role in SI-induced atrophy, while this response was blunted by 4 min of daily high-resistance electromechanical stimulation and was able to preserve most of the muscle mass. Although the protein anabolic pathway (IGF-1/PI3K/Akt) appears to play a minor role in regulating mass in the SI model, increased translational capacity may have contributed to mass preservation in response to isometric contractions.

The Effect of Path Length and Display Size on Memory for Spatial Information

2012 ◽  
Vol 59 (3) ◽  
pp. 147-152 ◽  
Author(s):  
Katherine Guérard ◽  
Sébastien Tremblay
Keyword(s):  
Path Length ◽  
Potential Role ◽  
Spatial Information ◽  
Recall Performance ◽  
Minor Role ◽  
Length Effect ◽  
Serial Memory ◽  
Fixed Reference ◽  
A Minor

In serial memory for spatial information, some studies showed that recall performance suffers when the distance between successive locations increases relatively to the size of the display in which they are presented (the path length effect; e.g., Parmentier et al., 2005) but not when distance is increased by enlarging the size of the display (e.g., Smyth & Scholey, 1994). In the present study, we examined the effect of varying the absolute and relative distance between to-be-remembered items on memory for spatial information. We manipulated path length using small (15″) and large (64″) screens within the same design. In two experiments, we showed that distance was disruptive mainly when it is varied relatively to a fixed reference frame, though increasing the size of the display also had a small deleterious effect on recall. The insertion of a retention interval did not influence these effects, suggesting that rehearsal plays a minor role in mediating the effects of distance on serial spatial memory. We discuss the potential role of perceptual organization in light of the pattern of results.

Use of Different Tissue Thromboplastins in the Control of Anticoagulant-Therapy

1958 ◽  
Vol 02 (05/06) ◽  
pp. 462-480 ◽  
Author(s):  
Marc Verstraete ◽  
Patricia A. Clark ◽  
Irving S. Wright
Keyword(s):  
Prothrombin Time ◽  
Anticoagulant Therapy ◽  
Factor Vii ◽  
Rabbit Brain ◽  
Minor Role ◽  
Rabbit Lung ◽  
Coagulation Mechanism ◽  
Time Test ◽  
The One ◽  
A Minor

SummaryAn analysis of the results of prothrombin time tests with different types of thromboplastins sheds some light on the problem why the administration of coumarin is difficult to standardize in different centers. Our present ideas on the subject, based on experimental data may be summarized as follows.Several factors of the clotting mechanism are influenced by coumarin derivatives. The action of some of these factors is by-passed in the 1-stage prothrombin time test. The decrease of the prothrombin and factor VII levels may be evaluated in the 1-stage prothrombin time determination (Quick-test). The prolongation of the prothrombin times are, however, predominantly due to the decrease of factor VII activity, the prothrombin content remaining around 50 per cent of normal during an adequate anticoagulant therapy. It is unlikely that this degree of depression of prothrombin is of major significance in interfering with the coagulation mechanism in the protection against thromboembolism. It may, however, play a minor role, which has yet to be evaluated quantitatively. An exact evaluation of factor VII is, therefore, important for the guidance of anticoagulant therapy and the method of choice is the one which is most sensitive to changes in factor VII concentration. The 1-stage prothrombin time test with a rabbit lung thromboplastin seems the most suitable method because rabbit brain preparations exhibit a factor VII-like activity that is not present in rabbit lung preparations.

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