bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of adenosine and its receptors in the vasodilatation induced in the cerebral cortex of the rat by systemic hypoxia
Authors: Coney A. M. , Marshall Janice M. 
Published: September 2004

In anaesthetized rats, we have examined the role of adenosine in vasodilatation evoked in the cerebral cortex by systemic hypoxia (breathing 8 % O2). Red cell flux was recorded from the surface of the exposed parietal cortex (CoRCF) by a laser Doppler probe, cortical vascular conductance (CoVC) being computed as CoRCF divided by mean arterial blood pressure. All agonists and antagonists were applied topically to the cortex.
Systemic hypoxia or adenosine application for 5 or 10 min, respectively, induced an increase in CoRCF and CoVC. These responses were substantially reduced by 8‐phenyltheophylline (8‐PT), an adenosine receptor antagonist which is non‐selective between the adenosine A1 and A2A receptor subtypes. By contrast, the adenosine receptor antagonist 8‐sulphophenyltheophylline (8‐SPT) which is similarly non‐selective, but unlike 8‐PT, does not cross the blood‐brain barrier, reduced the increases in CoRCF and CoVC induced by adenosine, but had no effect on those induced by hypoxia.
The A2A receptor agonist CGS21680 produced a substantial increase in CoRCF and CoVC, but the A1 receptor agonist 2‐chloro‐N6‐cyclopentyladenosine had minimal effects.
The A2A receptor antagonist ZM241385 reduced the increase in CoRCF and CoVC induced by adenosine and reduced the increase in CoRCF induced by hypoxia.
We propose that exogenous adenosine that is topically applied to the cerebral cortex produces vasodilatation by acting on A2A receptors on the vascular smooth muscle. However, during systemic hypoxia, we propose that adenosine is released from endothelial cells and acts on endothelial A2A receptors to produce the major part of the hypoxia‐induced dilatation in the cerebral cortex.
Fast voltage gating of Ca2+ release in frog skeletal muscle revealed by supercharging pulses
Authors: Kim Albert M. , Vergara Julio L. 
Published: September 2004

In single frog skeletal muscle fibres, we utilized supercharging voltage clamp command pulses to boost the rate of depolarization in the transverse tubular system (T‐system) such that 95 % of steady‐state potential is achieved in < 2 ms (as indicated by fluorescent potentiometric dye signals detected from a global illumination region). Signals detected near the edge of muscle fibres indicate that peripheral regions of the T‐system are not significantly overcompensated under these conditions.
We explored the impact of accelerating T‐system depolarization on voltage‐dependent events of excitation‐contraction (E‐C) coupling by measuring charge movement currents (CMCs) and Ca2+ fluorescence transients in response to both supercharging and conventional step pulses.
When compared with CMCs elicited by step pulses, supercharging CMCs are larger, and their kinetics more closely resemble those of gating current records reported for ionic channels. Furthermore, they decay bi‐exponentially (τfast range, 1.3‐1.8 ms; τslow range, 7.3‐11.9 ms), whereas step CMCs fall with a single exponential time course (τ range, 12.5‐26.7 ms).
Similarly, supercharging produces a distinct acceleration in Ca2+ release transients, which show little evidence of the voltage‐dependent onset latencies previously encountered using step pulses.
The use of this novel methodology in skeletal muscle unveils a previously undetected component of charge movement, the rapid, voltage‐dependent recruitment of which may provide the basis for understanding the fast gating of physiological E‐C coupling.
Distribution of photon absorption rates across the rat retina
Authors: Williams T. P. , Webbers J. P. P. , Giordano L. , Henderson R. P. 
Published: September 2004

An investigation into the distribution of light intensity across the rat retina was carried out on excised, intact rat eyes exposed to Ganzfeld illumination from a helium‐neon laser (543 nm).
Some of the light entering the eyes exits through the sclera where its intensity can be monitored with an optical ‘pick‐up’ that samples the intensity coming from a small region of external sclera and underlying retina. The spatial resolution of the pick‐up is such that it samples light that has passed through ca 2 % of the rods in the rat eye.
Some of the laser light is absorbed by the rod pigment, rhodopsin, which gradually bleaches. Bleaching in the retina, in turn, causes an exponential increase in intensity emanating from the sclera. By monitoring this intensity increase, we are able to measure two important parameters in a single bleaching run: the local rhodopsin concentration and the local intensity falling on the rods.
With an ocular transmission photometer, we have measured both the local intensity and the local rhodopsin concentration across wide regions of rat retina. Both pigmented and albino rats were studied.
The distributions of rhodopsin and intensity were both nearly uniform; consequently, the product, (rhodopsin concentration) × (intensity), was similarly nearly equal across the retina. This means that the initial rate of photon absorption is about the same at all retinal locations.
Interpreted in terms of photostasis (the regulation of daily photon catch), this means that the rate of photon absorption is about the same in each rod, viz. 14 400 photons absorbed per rod per second. Since this rate of absorption is sufficient to saturate the rod, one possible purpose of photostasis is to maintain the rod system in a saturated state during daylight hours.
Force‐velocity and power‐load curves in rat skinned cardiac myocytes
Authors: McDonald Kerry S. , Wolff Matthew R. , Moss Richard L. 
Published: September 2004

This study utilized a skinned myocyte preparation with low end compliance to examine force‐velocity and power‐load curves at 12 °C in myocytes from rat hearts.
In maximally activated myocyte preparations, shortening velocities appeared to remain constant during load clamps in which shortening took place over a sarcomere length range of ≈2.30‐2.00 μm. These results suggest that previously reported curvilinear length traces during load clamps of multicellular preparations were due in part to extracellular viscoelastic structures that give rise to restoring forces during myocardial shortening.
During submaximal Ca2+ activations, the velocity of shortening at low loads slowed and the time course of shortening became curvilinear, i.e. velocity progressively slowed as shortening continued. This result implies that cross‐bridge cycling kinetics are slower at low levels of activation and that an internal load arises during shortening of submaximally activated myocytes, perhaps due to slowly detaching cross‐bridges.
Reduced levels of activator Ca2+ also reduced maximal power output and increased the relative load at which power output was optimal. For a given absolute load, the shift has the effect of maintaining power output near the optimum level despite reductions in cross‐bridge number and force generating capability at lower levels of Ca2+.
Chemoafferent degeneration and carotid body hypoplasia following chronic hyperoxia in newborn rats
Authors: Erickson Jeffery T. , Mayer Catherine , Jawa Andrew , Ling Liming , Olson E. Burt , Vidruk Edward H. , Mitchell Gordon S. , Katz David M. 
Published: September 2004

To define the role of environmental oxygen in regulating postnatal maturation of the carotid body afferent pathway, light and electron microscopic methods were used to compare chemoafferent neurone survival and carotid body development in newborn rats reared from birth in normoxia (21 % O2) or chronic hyperoxia (60 % O2).
Four weeks of chronic hyperoxia resulted in a significant 41 % decrease in the number of unmyelinated axons in the carotid sinus nerve, compared with age‐matched normoxic controls. In contrast, the number of myelinated axons was unaffected by hyperoxic exposure.
Chemoafferent neurones, located in the glossopharyngeal petrosal ganglion, already exhibited degenerative changes following 1 week of hyperoxia from birth, indicating that even a relatively short hyperoxic exposure was sufficient to derange normal chemoafferent development. In contrast, no such changes were observed in the vagal nodose ganglion, demonstrating that the effect of high oxygen levels was specific to sensory neurones in the carotid body afferent pathway. Moreover, petrosal ganglion neurones were sensitive to hyperoxic exposure only during the early postnatal period.
Chemoafferent degeneration in chronically hyperoxic animals was accompanied by marked hypoplasia of the carotid body. In view of previous findings from our laboratory that chemoafferent neurones require trophic support from the carotid body for survival after birth, we propose that chemoafferent degeneration following chronic hyperoxia is due specifically to the loss of target tissue in the carotid body.
Influence of the hypothalamic paraventricular nucleus on cardiovascular neurones in the rostral ventrolateral medulla of the rat
Authors: Yang Z. , Coote J. H. 
Published: September 2004

The question of whether neurones in the paraventricular nucleus (PVN) of the hypothalamus have an excitatory influence on reticulo‐spinal vasomotor neurones of the rostral ventrolateral medulla (RVL) has been addressed in this study using anaesthetized rats.
Extracellular microelectrode recordings were made from sixty vasomotor neurones in the RVL, identified by their cardiac cycle‐related probability of discharge, by the decrease in activity in response to an increase in arterial blood pressure produced by intravenous phenylephrine and by the increase in activity in response to a decrease in blood pressure produced by intravenous nitroprusside.
More than 70 % of these RVL vasomotor neurones were identified as spinally projecting by antidromically activating their axons via a stimulating electrode in the lateral funiculus of the T2 or T10 segment of spinal cord.
Activation of neurones at different sites in the PVN with a microinjection of d,l‐homocysteic acid (DLH) elicited either pressor or depressor responses.
At PVN pressor sites fifteen RVL vasomotor neurones were shown to be activated prior to the blood pressure change. A further twenty RVL vasomotor neurones were observed to decrease activity following the blood pressure rise. At PVN depressor sites twelve RVL neurones were inhibited prior to the blood pressure change whereas another thirteen identified RVL neurones increased their discharge following the fall in blood pressure.
In three rats single shock electrical stimulation at a PVN pressor site, first identified with DLH, elicited a single or double action potential in thirteen RVL neurones with a latency of 27 ± 1 ms.
It is concluded that PVN neurones may elicit increases in blood pressure via excitatory connections with RVL‐spinal vasomotor neurones, and that other PVN neurones may elicit decreases in blood pressure via inhibitory connections with these RVL neurones.
Modulation of responses of feline γ‐motoneurones by noradrenaline, tizanidine and clonidine
Authors: Jankowska E. , Gladden M. H. , Czarkowska‐Bauch J. 
Published: September 2004

Effects of noradrenaline (NA) and the α2 agonists tizanidine and clonidine were tested on extracellularly recorded responses of γ‐motoneurones in deeply anaesthetized cats. Two types of responses were used; firstly, short latency phasic responses evoked by electrical stimulation of group II afferents in a muscle nerve and, secondly, tonic background discharges.
Responses evoked by group II muscle afferents were depressed when NA and tizanidine were applied ionophoretically close to a γ‐motoneurone and when clonidine was applied systemically. The number of spike potentials evoked by stimulation of these afferents decreased and their latencies increased. Responses evoked by flexor or extensor afferents in γ‐motoneurones innervating flexors or extensors were similarly depressed.
Tonic discharges were inconsistently and/or insignificantly affected by locally applied NA and tizanidine but were depressed by systemically applied clonidine.
Control tests indicate specific effects of NA and tizanidine application since similarly ionophoresed H+ ions did not change responses of γ‐motoneurones to stimulation of group II afferents, or only weakly enhanced their background discharges. Furthermore, serotonin ejected from a solution with a similar pH facilitated rather than depressed responses of γ‐motoneurones.
The results indicate that some antispastic effects of clonidine and tizanidine may be due to the depression of group II‐evoked responses of γ‐motoneurones, resulting in weaker responses of muscle spindles to muscle stretches.
Multiple pathways for L‐methionine transport in brush‐border membrane vesicles from chicken jejunum
Authors: Soriano‐García Juan F. , Torras‐Llort Mònica , Ferrer Ruth , Moretó Miquel 
Published: September 2004

The intestinal transport of L‐methionine has been investigated in brush‐border membrane vesicles isolated from the jejunum of 6‐week‐old chickens. L‐Methionine influx is mediated by passive diffusion and by Na+‐dependent and Na+‐independent carrier‐mediated mechanisms.
In the absence of Na+, cis‐inhibition experiments with neutral and cationic amino acids indicate that two transport components are involved in L‐methionine influx: one sensitive to L‐lysine and the other sensitive to 2‐aminobicyclo[2.2.1]heptane‐2‐carboxylic acid (BCH). The L‐lysine‐sensitive flux is strongly inhibited by L‐phenylalanine and can be broken down into two pathways, one sensitive to N‐ethylmaleimide (NEM) and the other to L‐glutamine and L‐cystine.
The kinetics of L‐methionine influx in Na+‐free conditions is described by a model involving three transport systems, here called a,b and c: systems a and b are able to interact with cationic amino acids but differ in their kinetic characteristics (system a: Km= 2.2 ± 0.3 μM and Vmax= 0.13 ± 0.005 pmol (mg protein)−1 (2 s)−1; system b: Km= 3.0 ± 0.3 mM and Vmax= 465 ± 4.3 pmol (mg protein)−1 (2 s)−1); system c is specific for neutral amino acids, has a Km of 1.29 ± 0.08 mM and a Vmax of 229 ± 5.0 pmol (mg protein)−1 (2 s)−1 and is sensitive to BCH inhibition.
The Na+‐dependent component can be inhibited by BCH and L‐phenylalanine but cannot interact either with cationic amino acids or with α‐(methylamino)isobutyrate (MeAIB).
The kinetic analysis of L‐methionine influx under a Na+ gradient confirms the activity of the above described transport systems a and b. System a is not affected by the presence of Na+ while system b shows a 3‐fold decrease in the Michaelis constant and a 1.4‐fold increase in Vmax. In the presence of Na+, the BCH‐sensitive component can be subdivided into two pathways: one corresponds to system c and the other is Na+ dependent and has a Km of 0.64 ± 0.013 mM and a Vmax of 391 ± 2.3 pmol (mg protein)−1 (2 s)−1.
It is concluded that L‐methionine is transported in the chicken jejunum by four transport systems, one with functional characteristics similar to those of system bo, + (system a); a second (system b) similar to system y+, which we suggest naming y+m to account for its high Vmax for L‐methionine transport in the absence of Na+; a third (system c) which is Na+ independent and has similar properties to system L; and a fourth showing Na+ dependence and tentatively identified with system B.
Na+‐K+ pump cycle during β‐adrenergic stimulation of adult rat cardiac myocytes
Authors: Dobretsov Maxim , Hastings Stephanie L. , Stimers Joseph R. 
Published: September 2004

The mechanisms underlying the increase in Na+‐K+ pump current (Ip) caused by adrenergic stimulation were investigated in cultured adult rat cardiac myocytes using the whole‐cell patch‐clamp technique at 31‐33 °C.
In myocytes perfused internally with 50 mm Na+ (0 Ki+, 20 nM Ca2+, caesium aspartate solution) and externally with 5.4 mm K+o, noradrenaline (NA) and isoprenaline (Iso) (1‐50 μm) stimulated Ip by 40‐45 %.
Na+‐dependent transient Ip measurements with 0 mm K+i and 0 mm K+o revealed no change in the total charge transferred by the Na+‐K+ pump during the conformational change, suggesting that the pump site density was not changed by adrenergic stimulation (2630 ± 370 pumps μm−2 in control and 2540 ± 190 pumps μm−2 in the presence of 10 μm NA).
With saturating Na+i or K+o (150 and 15‐20 mm, respectively), Ip was still stimulated by NA and Iso. Thus, there was no indication that adrenergic activation of the Na+‐K+ pump was mediated by accumulation of Na+i and K+o or changes in the Na+‐K+ pump affinity for Na+i and K+o.
Both Ip and its increase under adrenergic stimulation were found to depend on [K+]i. While steady‐state Ip decreased from 2.2 ± 0.1 to 1.2 ± 0.1 pA pF−1 (P < 0.05), the stimulation of Ip by 10 μm Iso increased from 0.38 ± 0.04 to 0.67 ± 0.06 pA pF−1 (P < 0.05) with an increase in [K+]i from 0 to 100 mm.
Under conditions that cause the Ip‐Vm (membrane potential) relationship to express a positive slope ([Na+]o, 150 mm; [K+]o, 5.4 mm) or a negative slope ([Na+]o, 0; [K+]o, 0.3 mm) Iso stimulated Ip with no change in the shape of Ip‐Vm curves. Thus, adrenergic stimulation of the Na+‐K+ pump was not due to an alteration of voltage‐dependent steps of the pump cycle.
Simulation of these data with a six‐step model of the Na+‐K+ pump cycle suggested that in rat ventricular myocytes a signal from adrenergic receptors increased the Na+‐K+ pump rate by modulating the rate of K+ de‐occlusion and release by the pump.
Reappearance of activity in the vestibular neurones of labyrinthectomized guinea‐pigs is not delayed by cycloheximide
Authors: Ris Laurence , Wattiez Ruddy , de Waele Catherine , Vidal Pierre‐Paul , Godaux Emile 
Published: September 2004

In mammals, unilateral labyrinthectomy induces an immediate depression of the resting discharges in the neurones of the ipsilateral vestibular nuclei. Later on, a spontaneous restoration of this activity occurs. The aim of the present study was to test the possibility that protein synthesis could be involved in the start of this process in the guinea‐pig.
Cycloheximide (CHX), a protein synthesis inhibitor, was injected intramuscularly 1 h before (30 mg kg−1) and 5 h after (15 mg kg−1) labyrinthectomy.
In a first group of animals, CHX was found to induce an inhibition of protein synthesis at levels ranging from 71 to 93 % for 9 h after labyrinthectomy.
In a second group of alert animals, we studied single unit activity of second‐order vestibular neurones. It was found that, in the 12–16 h post‐labyrinthectomy period, at a time when restoration began in guinea‐pigs not treated with CHX, the discharges in the labyrinthectomized group treated with CHX were not different from those observed in a previous study in labyrinthectomized animals not treated with CHX.
We conclude that protein synthesis is not required for the start of restoration of activity in the vestibular neurones deprived of their ipsilateral labyrinthine input.
Age and gender differences in excitation‐contraction coupling of the rat ventricle
Authors: Leblanc Normand , Chartier Denis , Gosselin Hugues , Rouleau Jean‐Lucien 
Published: September 2004

The objective of this study was to determine potential post‐pubertal gender‐specific differences in the contractility of papillary muscles, the electrophysiological properties and Ca2+ transients of freshly dissociated ventricular myocytes from the rat heart.
The contractions of rat papillary muscles from 2‐ to 14‐month‐old male and female rats were studied under isometric and isotonic conditions (29 °C). While the hearts of young (2–4 months) male and female rats displayed a similar contractile profile, papillary muscles of female rats aged 6 months and older exhibited smaller isometric and isotonic contractions, smaller maximal rates of tension and shortening development and decline (±DT/dt and ±DL/dt) velocities during both the onset and relaxation phases, and shorter contractions than age‐matched males.
To explore the possible cellular basis accounting for these differences, action potentials and macroscopic currents were recorded from freshly dissociated myocytes using the whole‐cell patch clamp technique (35 °C). Action potentials from male and female myocytes of 3‐ and 9‐month‐old rats did not vary as a function of age or gender. Consistent with these results, the magnitude (expressed in pA pF−1), voltage‐dependence and kinetics of the inward rectifier (IK1), transient outward (Ito) and sustained (IK) K+ currents displayed little, if any dependence on age or gender.
L‐type Ca2+ current (ICa(L)) measured in caesium‐loaded myocytes (35 °C) from male and female rats of 3, 6 and 9 months of age exhibited similar characteristics. In contrast, while Ca2+ transients measured with indo‐1 were similar between 3‐month‐old male and female rat myocytes, Ca2+ transients of 10‐month‐old female myocytes were significantly reduced and showed a diminished rate of relaxation in comparison with those recorded in male rats of similar age.
These results suggest that important gender‐related changes in excitation‐contraction coupling occur following puberty, probably due to differences in Ca2+ handling capabilities at the level of the sarcoplasmic reticulum.
Extracellular ATP raises cytosolic calcium and activates basolateral chloride conductance in Necturus proximal tubule
Authors: Bouyer Patrice , Paulais Marc , Cougnon Marc , Hulin Philippe , Anagnostopoulos Takis , Planelles Gabrielle 
Published: September 2004

Extracellular nucleotides modulate ionic transport mechanisms in various epithelia. In the present study, we investigated the effects of extracellular ATP on the intracellular free Ca2+ concentration ([Ca2+]i) and electrophysiological properties of Necturus maculosus proximal convoluted tubule (PCT).
ATP raised [Ca2+]i in microdissected fura‐2‐loaded PCTs (half‐maximal effect, ≈15 μmol l−1 ATP). The initial ATP‐induced changes in [Ca2+]i were not blunted by the removal of external Ca2+ nor by the presence of Ca2+ channel blockers, but were abolished by thapsigargin and suramin. The sequence for the potency of various agonists on [Ca2+]i was 2‐methylthioATP (2MeSATP) = ADP = ATP ≫ UTP, 2′,3′‐O‐(4‐benzoilbenzoil) ATP (BzATP), α,β‐methylene ATP (AMPCPP), adenosine.
In vivo electrophysiological measurements showed that 100 μmol l−1 peritubular ATP added to a Ringer solution reduced the basolateral cell membrane potential (Vm) and increased the cell membrane input conductance. In a low Cl− solution, this ATP‐induced depolarization was enhanced. These effects were inhibited by 1 mmol l−1SITS, consistent with the activation of a basolateral Cl− conductance.
The ATP‐induced change in Vm was reproduced by ADP but not by UTP or adenosine, and was prevented by suramin.
The ATP‐induced membrane depolarization was not influenced by thapsigargin, BAPTA AM, or staurosporin and was not reproduced by manoeuvres increasing [Ca2+]i or intracellular cAMP content.
We conclude that, in Necturus PCT, a P2y receptor mobilizes Ca2+ mainly from intracellular pools and increases a basolateral Cl− conductance, GCl. The activation of GCl occurs by a mechanism which is not related either to an increase in [Ca2+]i or cAMP content, or to PKC activation.