bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developmental changes in EPSC quantal size and quantal content at a central glutamatergic synapse in rat
Authors: Bellingham Mark C. , Lim Rebecca , Walmsley Bruce 
Published: September 2004

Developmental changes in amplitude and time course of single‐fibre‐evoked and spontaneous EPSCs mediated by AMPA and NMDA receptors at the endbulb‐bushy cell synapse of rats from 4 to 22 days of age were recorded using whole‐cell patch‐clamp methods inin vitroslices of cochlear nucleus.The mean conductance of the AMPA component of evoked EPSCs increased by 66 %, while that of the NMDA component decreased by 61 %, for 12‐ to 18‐day‐old rats cf. 4‐ to 11‐day‐old rats.The mean AMPA spontaneous EPSC conductance increased by 54 %, while mean NMDA spontaneous EPSC conductance decreased by 83 %, for 12‐ to 22‐day‐old rats cf. 4‐ to 11‐day‐old rats. The mean number of quanta contributing to peak evoked AMPA conductance also increased by 78 % in the older age group, after correction for the asynchrony of evoked quantal release.The decay time constant of spontaneous AMPA EPSCs showed a small decrease in older animals, while the decay time constant of spontaneous NMDA EPSCs was markedly decreased in older animals. The decay time constants of evoked NMDA EPSCs showed a quantitatively similar decrease to that of spontaneous NMDA EPSCs. This suggests that AMPA receptor subunit composition is unlikely to undergo developmental change, while NMDA receptor subunit composition may be substantially altered during synaptic maturation.These data are consistent with a developmentally increased efficacy of AMPA receptor‐mediated synaptic transmission at the endbulb‐bushy cell synapse, due to an increase in underlying AMPA‐mediated quantal size and content during the same period as a transient co‐localization of NMDA receptors.
Cannabinoids decrease excitatory synaptic transmission and impair long‐term depression in rat cerebellar Purkinje cells
Authors: Lévénès Carole , Daniel Hervé , Soubrié Philippe , Crépel Françis 
Published: September 2004

CB‐1 cannabinoid receptors are strongly expressed in the molecular layer of the cerebellar cortex. We have analysed, in patch‐clamped Purkinje cells (PCs) in rat cerebellar slices, the effect of the selective CB‐1 agonists WIN55,212‐2 and CP55,940 and of the selective CB‐1 antagonist SR141716‐A on excitatory synaptic transmission and synaptic plasticity.
Bath application of both agonists markedly depressed parallel fibre (PF) EPSCs. This effect was reversed by SR141716‐A. In contrast, responses of PCs to ionophoretic application of glutamate were not affected by WIN55,212‐2.
The coefficient of variation and the paired‐pulse facilitation of these PF‐mediated EPSCs increased in the presence of WIN55,212‐2.
WIN55,212‐2 decreased the frequency of miniature EPSCs and of asynchronous synaptic events evoked in the presence of strontium in the bath, but did not affect their amplitude.
WIN55,212‐2 did not change the excitability of PFs.
WIN55,212‐2 impaired long‐term depression induced by pairing protocols in PCs. This effect was antagonized by SR141716‐A. The same impairment of LTD was produced by 2‐chloroadenosine, a compound that decreases the probability of release of glutamate at PF‐PC synapses.
The present study demonstrates that cannabinoids inhibit synaptic transmission at PF‐PC synapses by decreasing the probability of release of glutamate, and thereby impair LTD. These two effects might represent a plausible cellular mechanism underlying cerebellar dysfunction caused by cannabinoids.
Altered regulation of natriuretic peptides in the rat heart by prenatal exposure to morphine
Authors: Ernest Sheila , Jankowski Marek , Mukaddam‐Daher Suhayla , Cusson Jean , Gutkowska Jolanta 
Published: September 2004

Both endogenous and exogenous opioids modulate blood pressure and cardiac function by stimulating cardiac synthesis of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP). Since morphine crosses the placental barrier, it could alter the ANF‐BNP system in the fetal heart. The aim of this study was to characterize cardiac natriuretic peptides in normal rat development and in rats prenatally exposed to morphine.
Female rats received either saline or morphine (10 or 20 mg kg−1 day−1) via osmotic minipumps during gestation. The effects of this treatment were investigated in offspring at 1, 4 and 22 days of age.
During maturation, atrial ANF and ANF mRNA increased by 3‐fold from birth to 3 weeks of age, but BNP and BNP mRNA tended to decrease. In the ventricles, both ANF and BNP content decreased at 3 weeks after birth, from 25.11 ± 3.6 to 0.81 ± 0.1 ng (P < 0.001), and from 3.36 ± 0.33 to 0.19 ± 0.01 ng (P < 0.001), respectively. However, whereas ventricular ANF mRNA decreased, BNP mRNA levels did not change during maturation. Prenatal exposure to morphine significantly increased ANF content in the left atria of 22‐day‐old rats, and in the right atria of 1‐, 4‐ and 22‐day‐old rats compared with age‐matched saline controls. In contrast, prenatal exposure to 20 mg kg−1 day−1 morphine significantly inhibited BNP and BNP mRNA in the ventricles at all ages studied.
These observations suggest that alterations in mRNA synthesis or stability and/or post‐translational processing of ANF and BNP occur in the heart during maturation, and that prenatal exposure to morphine alters cardiac production, and possibly release, of both peptides.
Possible involvement of the novel CPI‐17 protein in protein kinase C signal transduction of rabbit arterial smooth muscle
Authors: Li L. , Eto M. , Lee M. R. , Morita F. , Yazawa M. , Kitazawa T. 
Published: September 2004

CPI‐17 has recently been identified as a novel protein in vascular smooth muscle. In vitro, its phosphorylation and thiophosphorylation by protein kinase C (PKC) specifically inhibits the type 1 class of protein phosphatases, including myosin light chain (MLC) phosphatase.
Both of the phosphorylated CPI‐17 states dose‐dependently potentiated submaximal contractions at constant [Ca2+] in β‐escin‐permeabilized and Triton X‐100‐demembranated arterial smooth muscle, but produced no effect in intact and less intensely permeabilized (α‐toxin) tissue. Thiophosphorylated CPI‐17 (tp‐CPI) induced large contractions even under Ca2+‐free conditions and decreased Ca2+ EC50 by more than an order of magnitude. Unphosphorylated CPI‐17 produced minimal but significant effects.
tp‐CPI substantially increased the steady‐state MLC phosphorylation to Ca2+ ratios in β‐escin preparations.
tp‐CPI affected the kinetics of contraction and relaxation and of MLC phosphorylation and dephosphorylation in such a manner that indicates its major physiological effect is to inhibit MLC phosphatase.
Results from use of specific inhibitors in concurrence with tp‐CPI repudiate the involvement of general G proteins, rho A or PKC itself in the Ca2+ sensitization by tp‐CPI.
Our results indicate that phosphorylation of CPI‐17 by PKC stimulates binding of CPI‐17 to and subsequent inhibition of MLC phosphatase. This implies that CPI‐17 accounts largely for the heretofore unknown signalling pathway between PKC and inhibited MLC phosphatase.
Magnetic resonance imaging analysis of left ventricular function in normal and spontaneously hypertensive rats
Authors: Wise R. G. , Huang C. L.‐H. , Gresham G. A. , Al‐Shafei A. I. M. , Carpenter T. A. , Hall L. D. 
Published: September 2004

We have used magnetic resonance imaging (MRI) to examine acute morphological changes in the left ventricle throughout the cardiac cycle in normal Wistar Kyoto rats (WKY) and also to follow the development of chronic changes in spontaneously hypertensive rats (SHR). This involved the development of MRI and quantitative analysis techniques for characterizing contractile changes during the cardiac cycle.
Images of the cardiac anatomy in two age groups (8 and 12 weeks old) of young anaesthetized adult normal WKY and SHR were acquired in planes both parallel and perpendicular to the principal cardiac axis.
Complete coverage of the heart by imaging planes was achieved with high time resolution (13 ms), with typically 12 time frames in the cardiac cycle, using a short echo time (5 ms) multislice gradient‐echo imaging sequence. Imaging was synchronized to the R wave of the electrocardiogram.
The image slices could be reconstructed into complete geometrically and temporally coherent three‐dimensional data sets. Left ventricular (LV) volumes were thus reconstructed throughout the cardiac cycle by combining transverse cardiac image sections. This volume analysis revealed structural and functional differences between the normal WKY and SHR in both age groups of 8 and 12 weeks. Measurements from the cardiac images were additionally validated against histological measurements.
The SHR showed a raised LV end‐systolic volume and a correspondingly poorer ejection fraction as well as LV hypertrophy when compared with the controls. Left ventricular function in the SHR appeared stable between the two age groups.
We developed a simple geometrical model of the left ventricle based on a single longitudinal image section and successfully used this to describe some functional parameters of the left ventricle in the WKY and SHR. This geometrical model has the potential to greatly reduce the imaging time needed to study the beating heart in future serial investigations of cardiac physiology in rats.
Our experimental and analytical methods together form a powerful set of quantitative techniques which combine both imaging and functional analysis and will be applicable for future studies of chronic physiological changes in animal disease models.
Longitudinal distribution of components of excitatory synaptic input to motoneurones during swimming in young Xenopus tadpoles: experiments with antagonists
Authors: Zhao Fei‐Yue , Wolf Ervin , Roberts Alan 
Published: September 2004

Recent studies have revealed that the excitatory synaptic input to spinal motoneurones during fictive swimming in Xenopus tadpoles has three main components: glutamatergic (Glu) from premotor excitatory interneurones, nicotinic cholinergic (nACh) from more rostral motoneurones, and electrotonic coupling from neighbouring motoneurones. During swimming, these components sum to produce two kinds of excitation: phasic excitation (EPSPs) underlying spikes, and tonic depolarization.
We have investigated the longitudinal distribution of these excitatory synaptic inputs to presumed motoneurones at different positions along the spinal cord using intracellular recording techniques. Different antagonists (10 μm dihydro‐β‐erythroidine (DHβE) for nicotinic ACh receptors (nAChRs), 2 mM kynurenate (Kyn) for glutamate receptors (GluRs), and 100 μm Cd2+ for all chemical synapses) were microperfused very locally to unmask the relative contributions of these components to the total excitatory drive, and their distribution along the spinal cord during swimming.
If the potentials remaining when all chemical components were blocked by Cd2+ were subtracted from potentials recorded after blocking nAChRs and GluRs with DHβE plus Kyn, a small unidentified component was observed. This component was blocked by the specific AMPA antagonist 6‐nitro‐7‐sulphamoylbenzo(f)quinoxaline‐2,3‐dione (NBQX, 5 μm), so is glutamate mediated.
We used the potential measurements to calculate the relative synaptic conductances of the different synaptic inputs, and conclude that: (a) there is a rostral‐caudal gradient in input during EPSPs and tonic depolarization; (b) the glutamatergic component accounts for most of the excitation, and decreases caudally; (c) cholinergic and electrotonic components are relatively constant in different positions along the spinal cord; and (d) these two components provide an increasing proportion of the input in more caudal neurones.
We propose that the glutamate components of excitation are fundamental to rhythm generation in the brainstem and rostral cord, while the electrotonic and cholinergic components ensure that the central pattern generator activates motoneurones effectively in all parts of the spinal cord.
Oxygen‐sensing mechanisms are present in the chromaffin cells of the sheep adrenal medulla before birth
Authors: Rychkov G. Y. , Adams M. B. , McMillen I. C. , Roberts M. L. 
Published: September 2004

The ability of the fetal adrenal medulla to respond directly to hypoxaemia and secrete catecholamines before the development of a functional innervation of the gland is essential for intrauterine survival. The cellular mechanisms involved in this response to low PO2 are not known, although the presence of oxygen‐sensitive K+ channels in carotid body chemoreceptor cells and other sites suggests that these might underlie the chromaffin cell response.
Whole‐cell patch‐clamp techniques have been used to study K+ currents during normoxia and hypoxia in chromaffin cells isolated from the adrenal glands of fetal sheep.
Two types of chromaffin cells were observed, those with a fast inactivating K+ current and a larger capacitance and those with a delayed K+ current and smaller capacitance. No cell showed both types of current. The fast inactivating current showed voltage‐dependent inactivation and was blocked by 1 mM 4‐aminopyridine, characteristics of an IA‐type current. The delayed current had two components, a TEA‐sensitive, Ca2+‐dependent current and a component with the kinetic behaviour of a delayed rectifier.
Both types of current were oxygen sensitive. The IA‐type current was reduced by 27.4 ± 3.2 % when the PO2 was reduced to about 15 mmHg. With the delayed current, hypoxia reduced the amplitude by 26.9 ± 2.4 %, largely by reduction of the Ca2+‐dependent component.
In the presence of hypoxia, reduction in the amplitude of these oxygen‐sensitive K+ currents would increase the frequency and duration of action potentials, leading to increased activation of the L‐type Ca2+ channels, influx of Ca2+ and the subsequent secretion of catecholamines.
A trauma‐like elevation of plasma cytokines in humans in response to treadmill running
Authors: Ostrowski Kenneth , Hermann Claus , Bangash Aimal , Schjerling Peter , Nielsen Jakob Nis , Pedersen Bente Klarlund 
Published: September 2004

Elevated levels of cytokines, especially interleukin (IL)‐6 and IL‐1ra, can be measured in the plasma of athletes after exhaustive long term exercise.
The present study investigates the kinetics of several cytokines and chemokines in ten male athletes before, during and after 2.5 h of treadmill running at 75% of maximal oxygen consumption (VO2,max). Blood was sampled before, every half‐hour during running and every hour in the following 6 h recovery period.
The plasma concentration of IL‐6 increased after 30 min of running, and peaked at the end of running with a 25‐fold increase compared with the pre‐exercise value. IL‐1ra increased only after running, and peaked after 2 h of rest with an 18‐fold increase compared with the pre‐exercise value. No changes were found in the concentrations of IL‐1β, tumour necrosis factor (TNF)α, IL‐15 and macrophage inflammatory protein (MIP)‐1β, and the concentrations of IL‐8 and MIP‐1α were below detection limits.
The results suggest that very early events in exercise trigger the release of IL‐6, and that the cytokine response to exercise has similarities to that observed after trauma.
Nitric oxide modulates cholinergic reflex pathways to the longitudinal and circular muscle in the isolated guinea‐pig distal colon
Authors: Smith Terence K. , McCarron Sarah L. 
Published: September 2004

The involvement of nitric oxide (NO) in enteric neural pathways underlying reflex responses of the longitudinal muscle (LM) and circular muscle (CM) layers activated by mucosal stimulation was examined in the isolated guinea‐pig distal colon.
A segment of colon spanned two partitions (10 mm apart), which divided the organ bath into three chambers: a recording chamber where LM and CM tension was measured; a stimulation chamber where mucosal stimulation was applied; and a middle chamber separating them.
Brushing the mucosa anal and oral to the recording site evoked simultaneous oral contraction and anal relaxation of both the LM and CM.
N
ω‐nitro‐L‐argininel‐NA; 100 μm) or Nω‐nitro‐L‐arginine methyl ester (l‐NAME; 100 μm) applied to the middle chamber or stimulation chamber decreased the oral contractile response of the LM and CM (by about 30–40 %), but increased the anal relaxation (> 600 %) and exposed an anal contraction (> 1000 % increase) of both muscles. The addition of l‐NA to the recording chamber reduced the anal relaxation of the LM and CM and the anal contraction of the LM, but slightly increased the anal contraction of the CM.
S‐Nitroso‐N‐acetylpenicillamine (SNAP; 10 μm), an NO donor, reversed the effects of l‐NA in the middle or stimulation chambers.
1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ; 10 μm), a soluble guanylate cyclase inhibitor, mimicked the effects of l‐NAin the middle chamber or stimulation chamber, but these effects were not reversed by SNAP.
The oral contractile responses, and the anal relaxation and contractile responses of the LM and CM produced by l‐NA in the stimulation or middle chambers, were blocked by hexamethonium (300 μm) in any chamber. Atropine (1 μm) in the recording chamber reduced the contractile responses of the LM and CM.
In conclusion, endogenous NO facilitates and depresses release of acetylcholine from interneurons in ascending and descending nervous pathways, respectively. These NO effects are mediated through soluble guanylate cyclase in cholinergic interneurons
Membrane current noise in dark‐adapted and light‐adapted isolated retinal rods of the larval tiger salamander
Authors: Jones Gregor J. 
Published: September 2004

Low‐frequency light‐sensitive membrane current noise in isolated rod photoreceptors of the larval tiger salamander was recorded using suction electrodes, in the dark, and during light adaptation by backgrounds or by bleaching visual pigment.
In background light, noise variance increases and then decreases. For rods desensitized to similar levels by bleaching visual pigment, the noise variance either does not change (weak adaptation) or decreases (with stronger adaptation).
The power spectral density of the current noise in dark‐adapted rods shows a component with half‐power cut‐off frequency at about 0.1 Hz, attributed to spontaneous single events and continuous noise from dark phosphodiesterase activity. A second component, with half‐power cut‐off frequency at about 1 Hz, may be due to slow components in the light‐sensitive channel gating.
The power spectral density of the noise in background light is dominated by noise generated by the background. Background light adapts at least the first component of the noise seen in dark‐adapted cells. For cells desensitized by bleaching, light adaptation of both components of the dark‐adapted noise is observed.
The results confirm that the low‐frequency noise in dark‐adapted cells arises from the transduction mechanism of the rod, in that both components can be light adapted, and show that, for rods permanently desensitized by bleaching, the desensitization is not due to the presence of active visual pigment molecules similar to those produced by background light.
Mechanistic analyses of ion dependences in a high‐affinity human serotonin transport system in transfected murine fibroblast cells
Authors: Chang Albert S. , Lam Dominic M.‐K. 
Published: September 2004

A clonal cell line, L‐S1, has been identified from transfection of human genomic DNA into cultured mouse L‐M fibroblasts. Because this transfectant cell line stably expresses a high‐affinity serotonin (5‐HT) transport mechanism with kinetic and pharmacological properties comparable to those of other serotonin uptake systems, it was used to investigate the mechanistic involvement of Na+ and Cl− ions in the ligand binding and kinetic uptake processes of this system.
Intact transfectant cells, when incubated at low temperature (4 °C), enabled quantitative assessment of imipramine‐displaceable 5‐[3H]HT binding to the 5‐HT transport system. This binding activity is insensitive to the presence of various ligands specific for 5‐HT receptor subtypes.
Imipramine‐displaceable 5‐[3H]HT binding to intact L‐S1 cells was shown to be a Cl−‐dependent but Na+‐independent process. Chloride ions lack binding co‐operativity in facilitating ligand binding. Changes in external Cl− concentration altered the Kd but not the Bmax of binding.
The overall transport activity was observed to be highly dependent on both external Na+ and Cl− concentrations, characterized by a 5‐HT:Na+:Cl− coupling ratio of 1:1:1 per transport cycle. Alterations in the external concentrations of both Na+ and Cl− ions altered only the Km and not the Vmax of transport.
Both binding and kinetic results are consistent with kinetic modelling predictions of the Cl− ion in facilitating 5‐HT binding to the transport system, and of the Na+ ion in enabling translocation of bound 5‐HT across the plasma membrane. Thus, Na+ and Cl− ions facilitate mechanistically distinct and discernible functions in the transport cycle.
An in vitro study of the properties of vagal afferent fibres innervating the ferret oesophagus and stomach
Authors: Page Amanda J. , Blackshaw L. Ashley 
Published: September 2004

A novel preparation of the oesophagus with attached vagus nerve from the ferret maintained in vitro was used to study the properties of single vagal afferent nerve fibres with identified receptive fields.
Recordings were made from three types of gastro‐oesophageal vagal afferent fibres that were classified on the basis of their sensitivity to mechanical stimulation. There were those responding to mucosal stroking (mucosal receptors), to circular tension (tension receptors) and those responding to mucosal stroking and circular tension, which we have termed tension/mucosal (TM) receptors.
The conduction velocities for mucosal, TM and tension receptor fibres were 6.38 ± 1.22 m s−1 (n= 22), 6.20 ± 1.49 m s−1 (n= 13) and 5.33 ± 0.86 m s−1 (n= 22), respectively.
Receptive fields of afferents showed random topographical distribution by fibre type and conduction velocity. They were found mainly distal but also occasionally proximal to the point of vagal dissection.
Twenty‐eight per cent of mucosal, 63 % of TM and 43 % of tension receptors responded to one or more drugs or chemical stimuli applied to the receptive field.
In conclusion, this experimental preparation provides evidence for the existence of three types of oesophageal vagal afferent fibre, namely mucosal, tension and the newly identified tension/mucosal receptors.