The α2A adrenoceptor suppresses excitatory synaptic transmission to both excitatory and inhibitory neurons in layer 4 barrel cortex

Abstract

The mammalian neocortex is widely innervated by noradrenergic (NA) fibres from the locus coeruleus. To determine the effects of NA on vertical synaptic inputs to layer 4 (L4) cells from the ventrobasal (VB) thalamus and layer 2/3 (L2/3), thalamocortical slices were prepared and whole-cell recordings were made from L4 cells. Excitatory synaptic responses were evoked by electrical stimulation of the thalamus or L2/3 immediately above. Recorded cells were identified as regular spiking (RS), regular spiking non-pyramidal (RSNP) or fast spiking (FS) cells through their firing patterns in response to current injections. NA suppressed (∼50% of control) excitatory vertical inputs to all cell types in a dose-dependent manner. The presynaptic site of action of NA was suggested by three independent studies. First, responses caused by iontophoretically applied glutamate were not suppressed by NA. Second, paired pulse ratio was increased during NA suppression. Finally, a CV⁻² (CV: coefficient of variation) analysis was performed. The resultant diagonal alignment of the ratio of CV⁻² plotted against the ratio of the amplitude of postsynaptic responses suggests a presynaptic mechanism for the suppression. Experiments with phenylephrine (α1 agonist), prazosin (α1 antagonist), yohimbine (α2 antagonist) and propranolol (β antagonist) indicated that suppression was mediated by α2 adrenoceptor. To determine whether the α2A adrenoceptor subtype was involved, α2A adrenoceptor knockout mice were used. NA failed to suppress EPSCs in all cell types, suggesting an involvement of α2A adrenoceptor. Altogether, we concluded that NA suppresses vertical excitatory synaptic connections in L4 excitatory and inhibitory cells through presynaptic α2A adrenoceptor.

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The Effect of Acute Taurine Ingestion on Human Maximal Voluntary Muscle Contraction.

Purpose: To examine the effect of taurine ingestion on maximal voluntary muscle torque and power in trained male athletes with different caffeine habits. Methods: Fourteen male athletes aged 21.8 +/- 2.5 years were separated into caffeine and non-caffeine consumers to control for the effect of caffeine withdrawal on muscle function. On separate occasions, participants performed four isokinetic or three maximal isometric knee extensions with and without taurine (40 mg/kg body mass) following a double blind, counterbalanced design. Muscle contractile performances were compared between the first sets as well as between the sets where these variables scored best. Results: In response to isokinetic contraction, taurine treatment in the non-caffeine consumers resulted in a significant fall in first (-16.1%; p=0.013) and best peak torque (-5.0%; p=0.016) as well as in first (-17.7%; p=0.015) and best power output (-8.0%; p=0.008). In the caffeine consumers deprived of caffeine, taurine intake improved best power (5.2%; p=0.045). With respect to the isometric variables, there was a significant decrease in the first (-5.1%; p=0.002) and best peak torque (-4.3%; p=0.032) in the non-caffeine group, but no effect in the group of caffeine consumers deprived of caffeine. Taurine ingestion increased blood taurine levels, but had no effect on plasma amino acid levels. Conclusion: Taurine ingestion is detrimental to maximal voluntary muscle power and both maximal isokinetic and isometric peak torque in non-caffeine consumers, whereas taurine ingestion in caffeine-deprived caffeine consumers improves maximal voluntary muscle power but has not effect on other aspects of contractile performance. (C) 2017 American College of Sports Medicine

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Filamentation Involves Two Overlapping, but Distinct, Programs of Filamentation in the Pathogenic Fungus Candida albicans

The ability of the human pathogenic fungus Candida albicans to switch between yeast-like and filamentous forms of growth has long been linked to pathogenesis. Numerous environmental conditions, including growth at high temperatures, nutrient limitation, and exposure to serum, can trigger this morphological switch and are frequently used in in vitro models to identify genes with roles in filamentation. Previous work has suggested that differences exist between the various in vitro models both in the genetic requirements for filamentation and transcriptional responses to distinct filamentation-inducing media, but these differences had not been analyzed in detail. We compared 10 in vitro models for filamentation and found broad genetic and transcriptomic differences between model systems. The comparative analysis enabled the discovery of novel media-independent genetic requirements for filamentation as well as a core filamentation transcriptional profile. Our data also suggests that the physical environment drives distinct programs of filamentation in C. albicans, which has significant implications for filamentation in vivo.

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When disaster strikes, will your community be prepared?

If a disaster hits your community, will you be prepared? Are your leaders asking the right questions and taking the right steps to make sure your community could recover quickly and completely? Learn more about the flexible and adaptable resources from NIST's Community Resilience program that will help put your community on the path toward greater resilience.

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Title Page/Sections Editors

Publication date: October 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1860, Issue 10





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Commentary on "Measurement of the maximum oxygen uptake VO2max: VO2peak is no longer acceptable"

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Last Word on Point:Counterpoint

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Reply to Pettitt and Jamnicks letter in reference to: Measurement of the maximum oxygen uptake VO2max: VO2peak is no longer acceptable

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Last Word on Point:Counterpoint

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CORP: Improving the status quo for measuring whole body sweat losses

The measurement of whole body sweat losses (WBSL) is important to the study of body heat balance, body water balance, establishing guidelines for water and electrolyte consumption, and the study of metabolism and health. In principal, WBSL is measured by an acute change in body mass (BM) in response to a thermoregulatory sweating stimulus. In this Cores of Reproducibility in Physiology (CORP) review, we revisit several basic, but rarely discussed, assumptions important to WBSL research, including the common equivalences: mass = weight = water = sweat. Sources of large potential measurement errors are also discussed, as are best practices for avoiding them. The goal of this CORP review is to ultimately improve the accuracy, reproducibility, and application of WBSL research.

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Reduced collagen accumulation and augmented MMP-2 activity in left ventricle of old rats submitted to high-intensity resistance training

Progressive fibrosis is a hallmark of the aging heart. Age-related fibrosis is modulated by endurance exercise training; however, little is known concerning the influence of resistance training (RT). Therefore we investigated the chronic effects of high-intensity RT on age-associated alterations of left ventricle (LV) structure, collagen content, matrix metalloproteinase-2 (MMP-2), and extracellular matrix-related gene expression, including transforming growth factor-β (TGF-β). Young adult (3 mo) and aged (21 mo) male Wistar rats were submitted to a RT protocol (ladder climbing with 65, 85, 95, and 100% load), three times a week for 12 wk. Forty-eight hours posttraining, arterial systolic and diastolic pressure, LV end-diastolic pressure (LVEDP) and dP/dt were recorded. LV morphology, collagen deposition, and gene expression of type I (COL-I) and type III (COL-III) collagen, MMP-2, tissue inhibitor of metalloproteinases-1 (TIMP-1), and TGF-β1 were analyzed by quantitative reverse transcriptase-PCR. MMP-2 content was assessed by zymography. Increased collagen deposition was observed in LV from aged rats. These parameters were modulated by RT and were associated with increased MMP-2 activity and decreased COL-I, TGF-β1, and TIMP-1 mRNA content. Despite the effect of RT on collagen accumulation, there was no improvement on LVEDP and maximal negative LV dP/dt of aged rats. Cardiomyocyte diameter was preserved in all experimental conditions. In conclusion, RT attenuated age-associated collagen accumulation, concomitant to the increase in MMP-2 activity and decreased expression of COL-I, TGF-β1, and TIMP-1 in LV, illustrating a cardioprotective effect of RT on ventricular structure and function.

NEW & NOTEWORTHY We demonstrated the beneficial resistance-training effect against age-related left ventricle collagen accumulation in the left ventricle, which was associated with decreased type I collagen (COL-I), transforming growth factor-β1 (TGF-β1), and tissue inhibitor of metalloproteinases-1 (TIMP-1) gene expression and matrix metalloproteinase-2 (MMP-2) activity. Our findings suggest for the first time the potential effects of resistance training in modulating collagen accumulation and possibly fibrosis in the aging heart.

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Point:Counterpoint

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Sodium nitrate ingestion increases skeletal muscle nitrate content in humans

Nitrate (NO3–) ingestion has been shown to have vasoactive and ergogenic effects that have been attributed to increased nitric oxide (NO) production. Recent observations in rodents suggest that skeletal muscle tissue serves as an endogenous NO3– "reservoir." The present study determined NO3– contents in human skeletal muscle tissue in a postabsorptive state and following ingestion of a sodium nitrate bolus (NaNO₃). Seventeen male, type 2 diabetes patients (age 72 ± 1 yr; body mass index 26.5 ± 0.5 kg/m²; means ± SE) were randomized to ingest a dose of NaNO₃ (NIT; 9.3 mg NO3–/kg body wt) or placebo (PLA; 8.8 mg NaCl/kg body wt). Blood and muscle biopsy samples were taken before and up to 7 h following NO3– or placebo ingestion to assess NO3– [and plasma nitrite (NO3–)] concentrations. Additionally, basal plasma and muscle NO3– concentrations were assessed in 10 healthy young (CON-Y; age 21 ± 1 yr) and 10 healthy older (CON-O; age 75 ± 1 yr) control subjects. In all groups, baseline NO3– concentrations were higher in muscle (NIT, 57 ± 7; PLA, 61 ± 7; CON-Y, 80 ± 10; CON-O, 54 ± 6 µmol/l) than in plasma (NIT, 35 ± 3; PLA, 32 ± 3; CON-Y, 38 ± 3; CON-O, 33 ± 3 µmol/l; P ≤ 0.011). Ingestion of NaNO₃ resulted in a sustained increase in plasma NO3–, plasma NO3–, and muscle NO3– concentrations (up to 185 ± 25 µmol/l) in the NIT group (time effect P < 0.001) compared with PLA (treatment effect P < 0.05). In conclusion, basal NO3– concentrations are substantially higher in human skeletal muscle tissue compared with plasma. Ingestion of a bolus of dietary NO3– increases both plasma and muscle NO3– contents in humans.

NEW & NOTEWORTHY Literature of the pharmacokinetics following dietary nitrate ingestion is usually limited to the changes observed in plasma nitrate and nitrite concentrations. The present investigation assessed the skeletal muscle nitrate content in humans during the postabsorptive state, as well as following dietary nitrate ingestion. We show that basal nitrate content is higher in skeletal muscle tissue than in plasma and that ingestion of a dietary nitrate bolus strongly increases both plasma and muscle nitrate concentrations.

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Rebuttal from Billman on Point:Counterpoint: Exercise training-induced bradycardia

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Rebuttal from Boyett et al.

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Counterpoint: Exercise training-induced bradycardia: the case for enhanced parasympathetic regulation

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Point: Exercise training-induced bradycardia is caused by changes in intrinsic sinus node function

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CORP: The assessment of total hemoglobin mass by carbon monoxide rebreathing

In this Cores of Reproducibility in Physiology (CORP) article, we present the theory and practical aspects of the carbon monoxide (CO) rebreathing method for the determination of total hemoglobin mass in humans. With CO rebreathing, a small quantity of CO is diluted in O₂ and rebreathed for a specified time period, during which most of the CO is absorbed and bound to circulating hemoglobin. The dilution principle then allows calculation of the total number of circulating hemoglobin molecules based on the number of absorbed CO molecules and the resulting changes in the fraction of carboxyhemoglobin in blood. Total hemoglobin mass is derived by multiplication with the molar weight of hemoglobin. CO rebreathing has been used for >100 yr and has undergone steady improvement so that today excellent values in terms of accuracy and precision can be achieved if the methodological precautions are carefully followed.

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Time-course effects of aerobic physical training in the prevention of cigarette smoke-induced COPD

A previous study by our group showed that regular exercise training (ET) attenuated pulmonary injury in an experimental model of chronic exposure to cigarette smoke (CS) in mice, but the time-course effects of the mechanisms involved in this protection remain poorly understood. We evaluated the temporal effects of regular ET in an experimental model of chronic CS exposure. Male C57BL/6 mice were divided into four groups: Control (sedentary + air), Exercise (aerobic training + air), Smoke (sedentary + smoke), and Smoke + Exercise (aerobic training + smoke). Mice were exposed to CS and ET for 4, 8, or 12 wk. Exercise protected mice exposed to CS from emphysema and reductions in tissue damping and tissue elastance after 12 wk (P < 0.01). The total number of inflammatory cells in the bronchoalveolar lavage increased in the Smoke group, mainly due to the recruitment of macrophages after 4 wk, neutrophils and lymphocytes after 8 wk, and lymphocytes and macrophages after 12 wk (P < 0.01). Exercise attenuated this increase in mice exposed to CS. The protection conferred by exercise was mainly observed after exercise adaptation. Exercise increased IL-6 and IL-10 in the quadriceps and lungs (P < 0.05) after 12 wk. Total antioxidant capacity and SOD was increased and TNF-α and oxidants decreased in lungs of mice exposed to CS after 12 wk (P < 0.05). The protective effects of exercise against lung injury induced by cigarette smoke exposure suggests that anti-inflammatory mediators and antioxidant enzymes play important roles in chronic obstructive pulmonary disease development mainly after the exercise adaptation.

NEW & NOTEWORTHY These experiments investigated for the first time the temporal effects of regular moderate exercise training in cigarette smoke-induced chronic obstructive pulmonary disease. We demonstrate that aerobic conditioning had a protective effect in emphysema development induced by cigarette smoke exposure. This effect was most likely secondary to an effect of exercise on oxidant-antioxidant balance and anti-inflammatory mediators.

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Adaptations of motoneuron properties after weight-lifting training in rats

Resistance training, with repeated short-term and high-intensity exercises, is responsible for an increase in muscle mass and force. The aim of this study was to determine whether such training induces adaptations in the electrophysiological properties of motoneurons innervating the trained muscles and to relate these adaptive changes to previous observations made on motor unit contractile properties. The study was performed on adult male Wistar rats. Animals from the training group were subjected to a 5-wk voluntary progressive weight-lifting program, whereas control rats were restricted to standard cage activity. Intracellular recordings from lumbar spinal motoneurons were made under pentobarbital anesthesia. Membrane properties were measured, and rhythmic firing of motoneurons was analyzed. Strength training evoked adaptive changes in both slow- and fast-type motoneurons, indicating their increased excitability. A shorter spike duration, a higher input resistance, a lower rheobase, a decrease in the minimum current required to evoke rhythmic firing, an increase in the maximum frequencies of the early-state firing (ESF) and the steady-state firing (SSF), and an increase in the respective slopes of the frequency-current (f/I) relationship were observed in fast motoneurons of the trained group. The increase in the maximum ESF and SSF frequencies and an increase in the SSF f/I slope were also present in slow motoneurons. Higher maximum firing rates of motoneurons as well as higher discharge frequencies evoked at the same level of intracellular depolarization current imply higher levels of tetanic forces developed by motor units over the operating range of force production after strength training.

NEW & NOTEWORTHY Neuronal responses to weight-lifting training can be observed in altered properties of both slow and fast motoneurons. Motoneurons of trained animals are more excitable, require lower intracellular currents to evoke rhythmic firing, and have the ability to evoke higher maximum discharge frequencies during repetitive firing.

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Molecular mechanism for muscarinic M1 receptor-mediated endocytosis of TWIK-related acid-sensitive K+ 1 channels in rat adrenal medullary cells

Abstract

Activation of muscarinic receptor (mAChR) in rat adrenal medullary (AM) cells induces depolarization through the inhibition of TWIK-related acid-sensitive K⁺ (TASK)1 channels. Here, pharmacological and immunological approaches were used to elucidate the molecular mechanism for this mAChR-mediated inhibition. TASK1-like immunoreactive (IR) material was mainly located at the cell periphery in dissociated rat AM cells, and its majority was internalized in response to muscarine. The muscarine-induced inward current and translocation of TASK1 were suppressed by dynasore, a dynamin inhibitor. The muscarinic translocation was suppressed by MT7, a specific M₁ antagonist, and the dose response curves for muscarinic agonist-induced translocation were similar to those for the muscarinic inhibition of TASK1 currents. The muscarine-induced inward current and/or translocation of TASK1 were suppressed by inhibitors for phospholipase C (PLC), protein kinase C (PKC), and/or Src. TASK1 channels in AM cells and PC12 cells were transiently associated with Src and were tyrosine phosphorylated in response to muscarinic stimulation. After internalization, TASK1 channels were quickly dephosphorylated even while they remained in the cytoplasm. The cytoplasmic TASK1-like IR material quickly recycled back to the cell periphery after muscarine stimulation for 0.5 min, but not 10 min. We conclude that M₁R stimulation results in internalization of TASK1 channels through the PLC-PKC-Src pathway with the consequent tyrosine phosphorylation and that this M₁R-mediated internalization is at least in part responsible for muscarinic inhibition of TASK1 channels in rat AM cells.

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