bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal extraction of glutamine from plasma and whole blood: studies in dogs and rats
Authors: Vinay P. , Khoury N. , Soowamber M. , Gougoux A.
Published: April 2011

The change in plasma and blood cell pools of L-glutamine during a single pass through the kidney was studied in dogs and rats. It was shown that the glutamine content of blood cells does not change following one passage through the renal vascular bed in normal or acidotic dogs. Furthermore, an infusion of L-glutamine elevating by 10-fold the plasma concentration of this amino acid only minimally changed the blood cells' glutamine content. Therefore within the time frame of acute experiments, the dog blood cells can be assumed to be impermeable to glutamine in vivo. Accordingly, renal glutamine extraction can be measured using either whole blood or plasma arteriovenous difference in this species. However, the latter value is larger and therefore can be measured more accurately. In normal rats, no net renal glutamine extraction is measured. In contrast, a considerable renal glutamine uptake occurs in acidotic rats, 23% of the extracted glutamine coming from the blood cell pool. A load of glutamine in vivo significantly elevates both the plasma and the blood cell concentration. It is concluded (i) that the renal extraction of glutamine is best estimated using plasma arteriovenous difference in the dog, especially when the renal extraction is small; (ii) that whole blood measurements should be obtained in the rat.
A tribute to George I. Drummond, Ph.D.
Authors: Severson D. L.
Published: April 2011

not available
A novel cyclic GMP-lowering agent, LY83583, blocks carbachol-indiiced cyclic GMP elevation in rabbit atrial strips without blocking the negative inotropic effects of carbachol
Authors: Diamond Jack , Chu Evelyn B.
Published: April 2011

A novel cyclic GMP-lowering agent, LY83583(6-anilino-5,8-quinolinedkme), was used to investigate the possibility that increases in myocardial cyclic GMP levels are responsible for the negative inotropic effects of cholinergic agonists. Concentrations of carbachol from 0.3 to 3 μM elevated cyclic GMP levels in electrically paced rabbit atrial strips by 75 to 200% and decreased contractile force in the strips by 30 to 60%. Pretreatment of the muscles for 10 min with 10 μM LY83583 significantly lowered resting cyclic GMP levels and completely blocked the elevation of cyclic GMP by these concentrations of carbachol. However, the negative inotropic effects of carbachol were not blocked by the LY83583. These results indicate that the negative inotropic effects of carbachol in rabbit atrium are not mediated by increases in tissue levels of cyclic GMP.
A fast-twitch oxidative-glycolytic muscle with a robust inward calcium current
Authors: Carlsen Richard C. , Larson Douglas B. , Walsh Donal A.
Published: April 2011

This report describes the histochemical and physiological properties of a rat skeletal muscle with a robust activity-dependent slow inward Ca2+ current. The muscle, the flexor digitorum brevis (FDB), is a small plantar flexor from the hindfoot. It is a homogeneous muscle consisting of approximately 90% fast-twitch oxidative-glycolytic (type IIA) fibers. Stimulation of the FDB with repetitive stimulus trains (30 or 50 Hz for 330 ms, 1 train/s for 2–5 min) produced a slow increase in the base-line or resting tension of the muscle between trains. This progressive increase in resting tension appears to be due to the activation of voltage-dependent slow Ca2+ channels, since it could be eliminated (i) by stimulating the muscle in a medium containing 2 mM EGTA and without Ca2+, and (ii) by the addition of either Co2+ or verapamil. The presence of a slow current may be associated with an increase in K+ efflux as stimulation continues, and with a prolongation of relaxation time. We also propose that the slow Ca2+ current may contribute to the allosteric activation of phosphorylase kinase during muscle activity. The FDB provides an excellent preparation to investigate the regulation of muscle metabolism by intra- and extra-cellular Ca24 during exercise.
Adaptive changes in rat liver plasma membranes after chronic alcohol administration and its subsequent withdrawal
Authors: Lee Hung , Hosein E. A.
Published: April 2011

Rat hepatic plasma membranes isolated after chronic alcohol feeding displayed a different buoyant density range with a significantly increased peak density value when spun isopycnically in a 30–50% sucrose (w/w) gradient. This change persisted up to 48 h of withdrawal from alcohol. Analysis of membrane lipids revealed certain significant alterations in the phospholipids as well as the fatty acyl composition in individual phospholipids of the experimental plasma membranes. During withdrawal of alcohol for 48 h, all the alcohol-induced changes in the phospholipids returned to normal. Most initial changes in fatty acids reverted to the control composition during this time, but new changes in fatty acyl distribution were also observed. These were interpreted to represent readaptation to the withdrawal of the alcohol. It is not established how long this readaptation period lasts.
The receptors responsible for heat production in brown adipose tissue in the young rabbit
Authors: Harris W. H. , Moore L. A. , Yamashiro S.
Published: April 2011

It is known that adrenergic agonists stimulate thermogenesis in the brown fat of the young rabbit but the receptors responsible for mediating the response have not been identified. The infusion of either noradrenaline or isoproterenol (1–2 μg∙kg−1∙min−1) produced an increase in subcutaneous temperature (0.93 ± 0.15 and 1.22 ± 0.10 °C, respectively over the interscapular brown fat. At low doses (0.4 μg∙kg−1∙min−1) only isoproterenol was effective. The thermogenic response to isoproterenol was blocked by atenolol, a beta1-adrenergic antagonist. Neither salbutamol or terbutaline, both beta2-agonists, produced a temperature increase. Collectively, these data suggest that stimulation of beta1-adrenoceptor is primarily responsible for the thermogenic activity of brown fat in the rabbit. However, it was found that 53% of the increase in temperature could be blocked by prazosin, an alpha1-antagonist. Phentolamine was not effective as a blocker. Although a maximal brown fat thermogenic response can be achieved by stimulating the beta-adernoceptors, the alpha-adrenoceptors appear to play at least an auxiliary role in the young rabbit.
L-649,923, Sodium (βS*, γR*)-4-(3-(4-acetyl-3-hydroxy-2-propylphenoxy)-propylthio)-γ-hydroxy-β-methylbenzenebutanoate, a selective, orally active leukotriene receptor antagonist
Authors: Jones T. R. , Young R. , Champion E. , Charette L. , Denis D. , Ford-Hutchinson A. W. , Frenette R. , Gauthier J-Y. , Guindon Y. , Kakushima M. , Masson P. , McFarlane C. , Piechuta H. , Rokach J. , Zamboni R. , DeHaven R. N. , Maycock A. , Pong S. S.
Published: April 2011

L-649,923, Sodium (βs*, γR*)-4-(3-(4-acetyi-3-hydroxy-2-propylphenoxy)propylthio)-γ-hydroxy-β-methylbenzenebutanoate is a selective and competitive inhibitor of [3H]leukotriene D4 (Ki value of 400 nM) and to a lesser extent [3H]leukotriene C4 (Ki value of 8.6 μM) binding in guinea-pig lung homogenates. Functionally, it selectively antagonized contractions of guinea pig trachea induced by leukotriene C4, D4, E4, and F4 but not those induced by acetylcholine, histamine, serotonin, prostaglandin F2α, or U-44069 (stable endoperoxide analogue). Schild plot analysis indicated a competitive inhibition of contractions of guinea-pig ileum induced by leukotriene D4 (pA2 8.1) and contractions of guinea-pig trachea induced by leukotrienes E4 and F4 (pA2 7.1 and 6.9, respectively). In contrast, contractions of guinea-pig trachea induced by leukotrienes C4 (pA2 7.2; slope 0.6) and D4 (pA2 7.2; slope 0.7) were inhibited in a noncompetitive fashion. In vivo, intravenously administered L-649,923 selectively blocked bronchoconstriction induced in anesthetized guinea pigs by leukotriene C4 and D4 (ED50 values i.v. 0.38 and 0.26 mg/kg, respectively) but not that induced by histamine, arachidonic acid, serotonin, U-44069, or acetylcholine. Following intraduodenal administration, L-649,923, blocked leukotriene D4 induced bronchoconstriction (5 and 10 mg/kg). The present findings indicate that selective antagonists, such as L-649,923, may be useful for defining the role of leukotrienes in diseases such as bronchial asthma.
Two components of contraction in guinea pig papillary muscle
Authors: Honoré E. , Challice C. E. , Guilbault P. , Dupuis B.
Published: April 2011

Biphasic contractions were produced in guinea pig papillary muscle by inducing partial depolarization in a K+-rich solution (22 mM) containing 10−6 M isoproterenol. However, when the same conditions were applied to frog and rat, monophasic contractions were obtained. In the case of guinea pig, an increase in the beating frequency produced an increase in amplitude of the first component and a reduction of the second, while in frog and rat, only a decrease in the amplitude of contractions was recorded. Caffeine (10−3 M) eliminated the first component and increased the second in guinea pig, while in the case of rat and frog it decreased the amplitude of contractions. Procaine (10−3 M) suppressed the first component and decreased the second one. The contraction in frog appears to be similar to the second component of contraction in guinea pig, while in rat, the contraction is comparable with the first component in guinea pig. It is suggested that the calcium ions which activate the two components of contraction in guinea pig under the given experimental conditions may arise from two different sources.
Hepatic blood flow: accuracy of estimation from galactose clearances in cats
Authors: Burczynski F. J. , Greenway C. V.
Published: April 2011

Experiments were carried out to determine the accuracy and validity of estimations of hepatic blood flow from clearance data during infusions of galactose in anesthetized cats. Clearance calculations were compared directly with the measured hepatic blood flows using a hepatic venous long-circuit technique. This technique allowed direct measurement and alteration of hepatic blood flow and collection of arterial and mixed hepatic venous blood samples without depletion of the animal's blood volume. It was found that infusions of galactose could not be used to estimate accurately hepatic blood flow. Infusion rate could not be used as an estimate of hepatic or splanchnic uptake owing to substantial and variable extrasplanchnic uptake. As a result, estimated hepatic flows allowing for incomplete extraction overestimated the true flow. On the other hand, extraction was less than 100%. This caused systemic galactose clearance to underestimate hepatic blood flow. These errors could cancel each other giving an apparently good estimate of hepatic flow from systemic galactose clearance. This agreement was fortuitous and occurred only at a specific dose and blood flow. We conclude that in the absence of independent measurements of both extrasplanchnic uptake and splanchnic extraction of galactose, systemic galactose clearance is not a reliable measure of hepatic blood flow in anesthetized cats. Until proved otherwise, it seems likely that this is also true in humans.
6-Hydroxydopamine treatment enhances excitation of cultured cerebellar neurons by glutamate
Authors: Garber-Goldsman C. B. , Marshall K. C. , Bielajew C.
Published: April 2011

Explant cultures containing identifiable cerebellar cortical neurons and locus coeruleus neurons were treated with 500 μM 6-hydroxydopamine. At this concentration, locus coeruleus neurons were usually degenerated after 48 h, while the cerebellar cortical neurons had a normal appearance. Extracellular recording and iontophoresis of noradrenaline and glutamate were used to test for changes in electrical activity or neurotransmitter responsiveness of the cerebellar neurons. At 4–5 days following the toxin exposure, spontaneous spiking activity appeared similar to that in control cultures. Mean iontophoretic currents required to give noradrenaline-induced depressions of activity were somewhat lower for the toxin-treated cultures than for controls but not significantly so. The mean currents for glutamate excitations, however, were markedly lower in the treated cultures. Noradrenaline potentiations of glutamate responses were observed in both treated and control cultures. The greatly increased sensitivity of cerebellar neurons to glutamate does not seem related to degeneration of granule cells in the treated cultures but might be explained by disruption of astrocytic uptake mechanisms for glutamate.
Effects of 4-aminopyridine on the action potential and the after-hyper polarization of cat spinal motoneurons
Authors: Zhang Liang , Krnjevic Kresimir
Published: April 2011

In cats under pentobarbital anaesthesia, intramotoneuronal administrations of 4-aminopyridine significantly prolong the falling phase of the antidromic action potential but have much less effect on the orthodromic action potential. 4-aminopyridine probably blocks the fast K channels involved in the repolarization of the membrane and indirectly activates ionic channels through enhancement of synaptic transmission, also suggested by the potentiation of excitatory postsynaptic potentials. In many cells, 4-aminopyridine depresses the amplitude and prolongs the time course of the after-hyperpolarization; therefore 4-aminopyridine may also partly block Ca2+-activated K+ channels.
Nonstereoselective aspects of propranolol pharmacodynamics
Authors: Alkondon M. , Ray A. , Sen P.
Published: April 2011

Twenty years after its discovery, the β-adrenergic blocking agent propranolol continues to interest pharmacologists and clinicians. Its therapeutic profile has extended to areas beyond the purview of the cardiovascular system, and its ocular and central nervous system effects have been well documented. In addition, it still remains a very good pharmacological tool to map out the adrenergic β-receptors in the body, and stereoisomers of propranolol and other β-blockers serve as valuable agents to distinguish between the effects related to β-adrenoceptors and those which are not. The primary purpose of this review is to summarize the evidence indicating that β-adrenergic blocking agents lack stereoselectivity in some of their effects, including several of considerable therapeutic importance. Because many pharmacological actions of propranolol followed a nonsteroselective pattern, the involvement of β-adrenoceptors in them was questioned and this led to the search for alternate mechanisms to explain these effects. Studies with propranolol and some related drugs indicated the involvement of a cholinergic mechanism in their antiarrhythmic, ocular hypotensive and some central effects. Also, a presynaptic inhibitory effect at the skeletal neuromuscular junction has been suggested to explain the benefical effect of propranolol and other β-blockers in tremor. Biochemical studies with these drugs revealed their inhibitory action on the cholinesterase enzyme in blood and other tissues like myocardium and brain. It is thus hypothesized that modulation of cholinergic neurotransmission by propranolol could explain some of its nonstereoselective actions and open new vistas in propranolol pharmacodynamics.
Autonomic nervous system regulation of epicardial coronary vein systolic and diastolic blood velocity as measured by a laser Doppler velocimeter
Authors: Hellenbrand W. K. , Klassen G. A. , Armour J. A. , Sezerman O. , Paton B.
Published: April 2011

The velocity of blood in a major epicardial coronary vein accompanying the left anterior descending coronary artery of dogs was measured by means of a 140-μm fiber optic probe connected to a laser Doppler velocimeter. Right atrial pressure, left ventricular intramyocardial and cavity pressures, aortic pressure, as well as peripheral and central coronary venous pressures were compared with the velocity of blood measured in the epicardial coronary vein midway between the sites of the catheters measuring proximal and distal coronary vein pressures. During control conditions, coronary vein velocity was 14–18 cm/s during systole and 1.0–2.1 cm/s during diastole. Right stellate ganglion stimulation, norepinephrine or isoproterenol increased diastolic coronary vein velocity significantly, whereas left stellate ganglion stimulation did not. Average peak systolic velocity was not affected by these interventions. During these positive inotropic interventions, the peak coronary vein velocity usually occurred later in the cardiac cycle than during control conditions. Positive inotropic interventions appeared to decrease coronary vein velocity during systole and increase it during diastole. Left vagosympathetic trunk stimulation decreased diastolic but not systolic coronary vein velocity and usually caused peak coronary vein velocity to occur earlier in the cardiac cycle than during control states. Changes induced by vagosympathetic trunk stimulation usually occurred within one cardiac cycle. It is concluded that coronary vein blood velocity can be influenced by the autonomic nervous system.
Ca2+ channel ligand sensitive responses to the phorbol ester 12-O-tetradecanoylphorbol 13-acetate in vascular smooth muscle
Authors: Wei X. Y. , Triggle D. J.
Published: April 2011

The action of a tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA), on isolated rat aortic and tail artery strips has been characterized. TPA (10−9 – 10−7 M) produced a graded contraction developing maximum tension over 30–40 min. The contraction was irreversible and was not relaxed by prolonged washing with physiologic saline. Relaxation occurred upon washing with Ca2+-free saline but readdition of Ca2+ restored response. TPA was without significant effect in rat tail arteries in physiologic saline but produced responses in saline containing elevated K+ (15 mM). The protein kinase C inhibitor, CP-46,665-1 (4-aminomethyl-1-[2,3-(di-n-decyloxy)n-propyl]-4-phenylpiperidine dihydrochloride) (5 × 10−5 M), blocked the response to TPA but was without effect on responses to Bay K 8644 (2,6-dimethyl-3-carbomethoxy-5-nitro-4-(2-trifluoromethylphenyl) 1,4-dihydropyridine), KCl, phenylephrine, and B-HT 920 (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]azepin dihydrochloride). The calcium channel antagonist nifedipine and its analogue, 2,6-dimethyl-3,5-dicarbomethoxy-4-(3-cyanophenyl)-1,4-dihydropyridine, inhibited TPA responses with IC50 values of 9.28 × 10−9 and 1.96 × 10−7 M, respectively. Responses to Bay K 8644 in rat aorta were maximum in the presence of elevated KCl (10 mM), but TPA at concentrations of 10−9 and 3 × 10−9 M potentiated responses to Bay K 8644 in physiologic saline to levels approximating those in elevated K+ saline. TPA similarly potentiated responses to Ca2+ in Ca2+-free solution. In the presence of TPA, 10−8 and 3 × 10−8 M, responses to Ca2+ in nondepolarizing saline were potentiated to levels seen under depolarizing conditions. The present results suggest a relationship between protein kinase C and Ca2+ channel activation. However, alternative possibilities, including enhancement of the Ca2+ sensitivity of the contractile apparatus, may also contribute to the observed effects.
Luteinizing hormone release in intact and castrate rams is altered with immunoneutralization of endogenous estradiol
Authors: Sanford Lee M.
Published: April 2011

Changes in the dynamics of luteinizing hormone (LH) release in the adult ram following immunoneutralization of endogenous estradiol were investigated. Castrate rams were actively immunized against estradiol-6 – bovine serum albumin for 7 months and then their patterns of episodic LH release and LH response to multiple injections of gonadotropin-releasing hormone (GnRH, two 5-μg doses given iv 2 h apart) were assessed (April). In comparison with control rams immunized against rabbit gamma globulin, estradiol-immunized rams (antibody titre ~1:5000) exhibited more frequent LH releases (11.7 ± 0.3 vs. 9.3 ± 0.8 pulses/8 h, P < 0.05) and a greater LH response to the first GnRH injection (peak Δ value 190 ± 8 vs. 130 ± 25 ng/mL, P < 0.01). Estradiol antiserum collected from the castrate rams was used in the passive immunization of intact rams (antibody titre ~1:200) for 1 month (beginning mid-July). Although episodic LH release was always similar for control and immunized rams, testosterone levels in the latter group increased approximately 150%. In contrast with the castrate ram response, GnRH treatment (two 5-μg doses given iv 80 min apart) produced a "self-priming" effect on LH release in the intact rams, an effect that was dampened with estradiol immunoneutralization. Consequently, peak 2: peak 1 ratios for Δ value and 80-min mean incremental increase were much smaller (P < 0.01) for the immunized rams (~2:1 vs. 4:1 for the control rams). Data indicate that estradiol is (i) biologically active at the level of the hypothalamic-pituitary axis in the castrate ram and (ii) involved in maintaining the self-priming effect of GnRH on LH release in the intact ram.
Urinary concentrating defect in glutathione-depleted rats
Authors: Torres Adriana M. , Rodríguez Joaquín V. , Elías María M.
Published: April 2011

The effect of an acute depletion of glutathione by diethyl maleate injection on renal concentrating function was examined in rats. The parameters tested were the concentration and dilution of urine, applying conventional clearance techniques. Tissue osmolality and Na+-K+ ATPase activity were also measured. Diethyl maleate treated rats showed a diminished renal glutathione concentration and an impairment in the glomerular filtration rate and in electrolyte and water excretion. Treated rats also showed a diminished urine-to-plasma osmolality ratio as compared with controls. The studies on free water formation revealed a marked difference between groups; these data were supported with a diminished medullary Na+–K+ ATPase and a diminished corticomedullary osmolality gradient in the treated rats. The studies suggest that one area of target cells of glutathione depletion is that of the ascending limb of Henle's loop.
Isolation of an N-alkylprotoporphyrin IX from chick embryo livers following the administration of 3,5-diethoxycarbonyl-1,4-dihydro-4-ethyl-2,6-dimethylpyridine
Authors: McCluskey S. A. , Sutherland E. P. , Racz W. J. , Marks G. S.
Published: April 2011

The ferrochelatase-lowering activity of 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine (DDC) analogues in chick embryo hepatocyte culture has been assumed to be due to the formation of an N-alkylprotoporphyrin IX. This assumption required confirmation. For this reason the 4-ethyl analogue of DDC was administered to phenobarbital-pretreated 19-day-old chick embryos. This resulted in hepatic accumulation of a green pigment with ferrochelatase-inhibitory activity. The green pigment was identified as an N-alkylprotoporphyrin IX by comparison of the electronic absorption spectra of its dimethyl ester and Zn complex with the corresponding spectra obtained from synthetic N-ethylprotoporphyrin IX.
Adrenomedullary pressor responses to stimulation of the rostral hypothalamus in the rat: influence of adrenaline-induced vasodilation and reflex cardioinhibition
Authors: Gauthier Pierre
Published: April 2011

Electrical stimulation (100 Hz, 1 ms, 150 μA, 10 s) of the anterior hypothalamus in chloralose-anesthetized rats evoked a biphasic pressor response consisting of an initial sharp rise in arterial pressure at the onset of stimulation, followed by a second elevation after cessation of the stimulus. This response was accompanied by an increase in plasma noradrenaline and adrenaline levels. Peripheral sympathectomy with guanethidine selectively abolished the primary phase of the biphasic pressor response, while bilateral removal of the adrenal medulla eliminated only the secondary component. After α-adrenergic blockade with phentolamine, the primary phase of the stimulation-induced response was reduced while the secondary pressor component was blocked and replaced by a significant hypotension. The intravenous administration of sotalol enhanced the secondary pressor component without affecting the stimulation-induced plasma noradrenaline and adrenaline responses. After treatment with atropine, the secondary pressor effect was also potentiated, as the reflex bradycardia normally associated with the response was eliminated. A subsequent administration of sotalol in these rats further potentiated the secondary pressor component to stimulation. In rats treated with atropine and sotalol, the sympathetic vasomotor and the adrenomedullary pressor responses could be dissociated according to thresholds and stimulus frequency or current–response characteristics. The results suggest that in intact rats, adrenaline-induced vasodilation and reflex cardiac inhibition contribute to either reduce or mask the adrenomedullary component of the biphasic pressor response evoked by stimulation of the anterior hypothalamus. The study also raises the hypothesis of a dual regulation of both components of the sympathetic system in the anterior hypothalamic region.
Spatial Representations and Sensorimotor Transformations
Authors: Kalaska John , Smith Allan , Lamarre Yves
Published: April 2011

Each year, the Centre de recherche en sciences neurologiques of the Université de Montréal organizes a symposium on a topic in the neurosciences. For the IXth International Symposium, the theme chosen was "Spatial Representations and Sensorimotor Transformations."Many of the diverse functions performed by the central nervous system have an important spatial component in common. For instance, there are neural mechanisms for the analysis and perception of the three-dimensional structure of visual space, such as the location, form, and movement of objects in the visual environment. There exist processes to determine the spatial location of auditory stimuli. One can also regard the body as an "internal" space for which mechanisms have evolved for the kinesthetic perception of the position and movement of body parts relative to one another, and for the position and orientation of the body within its immediate external environment. Motor control also requires spatial information, since many movements of the eyes, head, and limbs follow specific paths or are aimed at the specific spatial location of an object as signalled by sensory processes.One can argue, therefore, that a major aspect of the functioning of the brain involves the generation of many different spatial representations, and the exchange of information among them. Each of these neural representations provides a spatial coordinate framework whose coordinate axes are based on certain types of information. For instance, movement of the limb toward an object can be described equally well in several different coordinate systems, such as those based on its spatial path, its dynamics (the direction and level of forces, torques, and external loads), or the muscle activity by which it is achieved. A better understanding of the coordinates in which the CNS codes these various types of information will provide a better appreciation of the neural mechanisms generating the spatial representations. It will also provide a clearer understanding of the transformations that must occur to relay information between sensory and motor representations, which permit an animal to interact successfully with its environment.The participants at this Symposium were invited to examine some of these issues as they pertain to the somatic and visual systems.
Proprioceptors and their contribution to somatosensory mapping; complex messages require complex processing
Authors: Matthews Peter B. C.
Published: April 2011

This review of other people's work concentrates on two matters. First, which of the various receptors are chiefly involved in creating the central representations or maps of the body that both underlie the conscious perception of our body image and are needed to control our motor performance. Second, how are these relatively well-charted signals used in sensorimotor mapping, with particular attention paid to various human psychophysical observations and illusions that throw light on the central integrative mechanisms involved. Detailed citation is largely restricted to developments since earlier reviews.
The representation of arm movements in postcentral and parietal cortex
Authors: Kalaska John F.
Published: April 2011

Considerable experimental evidence supports the hypothesis that the neocortical processes underlying kinesthetic sensation form a hierarchical series of cells signalling increasingly complex patterns of movement of the body. However, this view has been criticized and the data lack quantitative verification under controlled conditions. These studies have also typically used one-dimensional (reciprocal) movements, even of multiple degree-of-freedom joints such as the wrist or shoulder, and have been restricted to passive movements. This latter limitation is particularly critical, since the response of many muscle receptors is affected by fusimotor activity while that of many articular receptors is sensitive to the level of muscle contractile activity. Both factors introduce significant kinesthetic ambiguity to the signals arising from these receptors during active movement. This ambiguity is evident in the discharge of primary somatosensory cortex proprioceptive cells. Studies in area 5 show that single cells signal shoulder joint movements in the form of broad directional tuning curves. The pattern of activity of the entire population encodes movement direction. The cells appear to encode spatial aspects of movement unambiguously, since their discharge is relatively insensitive to the changes in muscle activity required to produce the same movements under different load conditions. It is not yet certain whether the somesthetic activity in area 5 is a kinesthetic representation that is sequential to and hierarchically superior to that in SI, or whether it is a parallel representation with separate and distinct functions.
Planning and execution of multijoint movements
Authors: Hogan Neville
Published: April 2011

This paper reviews some recent studies related to the generation of simple multijoint arm movements. Two principal issues are considered. The first concern is how movements are represented internally by the central nervous system. There are many possible sets of coordinates that could be used to represent arm movements. Two of the possibilities are reviewed: representation in terms of joint angular motions versus representation in terms of motions of the hand in external space coordinates. A second concern is the transformation from intention to action: how is an internal representation of motion expressed by the neuromuscular system? The computational complexity of this problem is reviewed. A way in which the mechanics of the neuromuscular system could be exploited to simplify this problem is discussed.
Interactions between plasma proteins and pulmonary surfactant: surface balance studies
Authors: Keough Kevin M. W. , Parsons Caroline S. , Phang P. Terence , Tweeddale Martin G.
Published: April 2011

The influence of human fibrinogen, α-globulin, and albumin on the properties of monolayers of pulmonary surfactant under dynamic compression and expansion has been studied at 37 °C. Each of the proteins altered some of the properties of the normal compression and expansion isotherms of surfactant such that characteristics deemed desirable for proper lung function were impaired. The order of potency of these effects was fibrinogen>globulin>albumin. The proteins (a) decreased the maximum surface pressure (equivalent to the minimum surface tension) which the surfactant monolayers attained on compression, (b) decreased the areas occupied per mole of lipid phosphorus when the monolayers were at surface tensions of 20 and 12 mN∙m−1, (c) reduced the areas of the hysteresis between compression and expansion isotherms, and (d) decreased the rate of change of surface tension with area at the point of initial expansion of the monolayers. The proteins might compete with surfactant lipid for available space at the interface, especially at low film compression. They might also enhance the desorption of lipid from the monolayer. The findings are consistent with the loss of pulmonary function and presence of edema that occur in adult respiratory distress syndrome being contributed to by plasma proteins interfering with surfactant function.
Nitrendipine blocks high potassium contractures but not twitches in rat skeletal muscle
Authors: Frank G. B. , Konya L. , Sudha T. Subrahmanyam
Published: April 2011

The effects of the organic calcium channel blocker nitrendipine was tested on electrically evoked twitches and on potassium depolarization-induced contractures of rat lumbricalis muscles. Nitrendipine (10−7 to 5 × 10−5 M) blocked only the potassium contractures. It was concluded that blocking calcium uptake through the slow voltage-senstitive calcium channels during potassium depolarization blocks the mechanical response of the muscle. Thus extracellular calcium ions are required for the excitation–contraction (E–C) coupling during depolarization contractures. On the other hand, electrically evoked twitches were not affected by nitrendipine; therefore, extracellular calcium ions entering via the slow voltage-sensitive channels are not required for E–C coupling during the twitch.
Aftercontractions and excitation–contraction coupling in rat cardiac muscle
Authors: Keurs Henk E.D.J. ter , Backx Peter H. , Tombe Peter P. de , Mulder Barbara J.
Published: April 2011

Calcium loading in cardiac muscle may cause spontaneous contractions (SC). We observed that SC move at a constant rate (Vsc) through isolated rat myocytes and trabeculae. Factors that influence the properties of SC were studied with Nomarsky microscopy and laser diffraction techniques. Myocytes and trabeculae were superfused with Krebs–Henseleit solution (21 °C, pH 7.35; Ca2+, 0.5–7 mM). Vsc in myocytes and within cells of trabeculae ranged between 50 and 150 μm/s. After a train of 3–25 stimuli at 2 Hz, SC in trabeculae started at a site of damage in a region 250 μm in length throughout the muscle. This regional contraction then moved at a constant rate (Vsc) along the length of the muscle. Vsc increased from 0.1 to 15 mm/s with stimulation and Ca2+. Under conditions of calcium loading, spontaneous twitches also occurred throughout the trabeculae, often as triggered arrhythmias. These twitches were always preceded by SC. The range of observed Vsc could be predicted by the Ca2+-induced Ca2+ release hypothesis. We postulated that the contraction propagates by virtue of focal calcium release from the sarcoplasmic reticulum (SR) and we simulated this process together with the processes of diffusion into the cytosol, binding to calmodulin and troponin, sequestration by the SR, and subsequent induction of Ca2+ release from the adjacent SR. The parameters used for the kinetics of binding, release, and sequestration were obtained from those reported in the literature. The minimal and maximal velocities derived from the simulation were 0.09 and 25 mm/s, respectively. The method of solution involved writing the diffusion equation as a difference equation in the spatial coordinates. Thus, bounded, coupled, and ordinary differential equations in time were generated. The coupled equations were solved by using Gear's sixth order predictor–corrector algorithm for stiff equations along with reflective boundaries. These calculations were performed on the Cyber 205 at the University of Calgary. Our results are consistent with the assumptions that Ca2+ loading causes an increase in intracellular Ca2+ concentration, a decrease in the relative threshold for induction of release, and an increase in the amount and rate of Ca2+ released, and hence causes a higher propagation velocity.
Effect of long-term and short-term diabetes on the parathyroid hormone sensitive rat renal adenylate cyclase: correlation with vitamin D metabolism
Authors: Rao L. G. , Kung M. S.
Published: April 2011

In short-term experiments, male Wistar rats were made diabetic for 10 days with a single injection of streptozotocin (65 mg/kg body weight). One group of diabetic rats was treated with insulin for 3 days prior to sacrifice. In long-term experiments, vitamin D replete or vitamin D depleted rats were made diabetic for 6 weeks. Criteria for diabetes were loss of weight, glycosuria (Tes-Tape), and hyperglycemia. In long-term diabetic rats the activity of renal mitochondrial 25-hydroxyvitamin D3 (25-(OH)D3) 1α-hydroxylase was significantly decreased and that of 25-(OH)D3 24-hydroxylase increased. However, the parathyroid hormone (PTH) sensitive renal adenylate cyclase activity of diabetic rats was not different from that of the nondiabetic rats in either the vitamin D replete group or the vitamin D depleted group. On the other hand, the PTH-sensitive renal adenylate cyclase activity was significantly higher in short-term diabetic rats than in control and insulin-treated rats. These differences were observed at doses of 10−8 to 10−5 M of PTH. This study has demonstrated for the first time that there are differences in the PTH-sensitive adenylate cyclase response between long-term and short-term diabetic rats. The hypersensitivity to PTH of the renal adenylate cyclase observed in short-term diabetic rats probably represents a response to insulin deficiency during the early development of diabetes mellitus in the rats.
Depression of potassium-evoked striatal acetylcholine release by δ-receptor activation: inhibition by cholinoactive agents
Authors: Ruzicka Bianca B. , Jhamandas Khem
Published: April 2011

To examine the role of δ-opioid receptors in the modulation of striatal acetylcholine (ACh) release, the action of D-Pen2,L-Pen5-enkephalin, a selective δ-opioid receptor agonist, was tested on [3H]ACh release from slices of the rat caudate–putamen. Slices, incubated with [3H]choline, were superfused with a physiological buffer and stimulated twice by exposure to a high potassium (K+) concentration. In the absence of a cholinesterase inhibitor, 1 μM D-Pen2,L-Pen5-enkephalin produced a 46 and 35% decrease in the release of [3H]ACh evoked by 15 and 25 mM K+, respectively. The depressant action of the enkephalin analogue was concentration dependent, with a maximal effect on K+-evoked [3H]ACh release occurring at 1.0 μM, and was completely blocked in the presence of the δ-opioid receptor selective antagonist, ICI 174864 (1 μM). In the presence of the cholinesterase inhibitors physostigmine (10 μM) and neostigmine (10 μM), or the muscarinic receptor agonist oxotremorine (10 μM), D-Pen2,L-Pen5-enkephalin did not depress the K+-evoked release of [3H]ACh. Atropine (1 μM) blocked the inhibitory effect of physostigmine on the depressant action of D-Pen2,L-Pen5-enkephalin. The results of this study indicate that δ-opioid receptor activation is associated with an inhibition of striatal ACh release, but this opioid–cholinergic interaction is not apparent under conditions of presynaptic muscarinic receptor activation.
Effect of colchicine on alkaline triglyceride lipase activity and triglyceride content in rat skeletal muscle
Authors: Gorski J. , Miller W. C. , Palmer W. K. , Oscai L. B.
Published: April 2011

One purpose of this study was to determine if colchicine increased intracellular alkaline triglyceride (TG) lipase activity above control levels in rat skeletal muscle. The second aim was to determine the effects of colchicine treatment on the concentration of TG in skeletal muscle. The results show that colchicine was a potent inducer of alkaline TG lipase activity, increasing enzyme activity approximately twofold in slow-twitch red, fast-twitch red, and fast-twitch white muscle types. It was found that in slow-twitch red soleus and fast-twitch red vastus, the two muscle groups with the highest levels of enzyme activity, 76% or more of enzyme activity resides in the intracellular compartment. These results provide evidence that colchicine blocks the export of alkaline TG lipase from skeletal muscle cells similar to that seen in the heart. The finding that TG were reduced at a time when enzyme activity was elevated suggests that intracellular alkaline TG lipase may be playing a role in the hydrolysis of the intramuscular TG droplet.
Metabolic effects of valproate on dog renal cortical tubules
Authors: Gougoux André , Vinay Patrick
Published: April 2011

The effect of valproate (0.01–10 mM), an antiepileptic drug inducing hyperammonemia in humans, was studied in vitro on a suspension of renal cortical tubules (> 85% proximal tubules) obtained from six normal dogs. When these tubules were incubated with 1 mM glutamine, the addition of valproate accelerated glutamine uptake, ammoniagenesis, and the production of alanine, lactate, and pyruvate. With 5 mM glutamine, a rise in glutamate accumulation, a much greater synthesis of alanine, an important aspartate production, and a striking accumulation of lactate and pyruvate were observed. With 1 or 5 mM lactate, lactate utilization and gluconeogenesis were markedly reduced with increasing concentrations of valproate. Oxygen consumption was reduced by only 15–20% by 10 mM valproate. The accelerated glutamine utilization resulting from valproate could not be prevented by aminooxyacetate, an inhibitor of transamination. Valproate also reduced various enzymatic activities, a finding that could not explain its metabolic effects. Four sites of action may explain these various metabolic changes: (i) a stimulation of mitochondrial glutamine transport, (ii) an increase in the flux of glutamate to malate, and (iii) a reduction in the net oxidation of pyruvate and (iv) in the flux through pyruvate carboxylase.Key words: hyperammonemia, glutamine metabolism, ammoniagenesis, pyruvate, lactate metabolism.
Activation by curare of acetylcholine receptor channels in a murine skeletal muscle cell line
Authors: Morris Catherine E. , Montpetit Madeleine R. , Sigurdson Wade J. , Iwasa Kuni
Published: April 2011

Curare action on nicotinic acetylcholine receptors has a number of facets, of which the best known is competitive antagonism. Here we describe the weak agonist action of 10−5 M curare on the murine skeletal muscle cell line, G8. Although curare induces no depolarization in G8 cells, single-channel recordings reveal short-lived curare-induced currents. A feature of these brief events is the multiplicity of conductance levels (of the four levels with conductances of 48, 37, 14, and 6 pS, none had a lifetime greater than 1.5 ms). Most well-resolved events (about 17% of which are to a subconductance) last less than 0.5 ms, with activation occurring predominantly as isolated events rather than in bursts. Agonism is not, however, a high probability action for curare: calculations based on the frequency of events at half-saturating conditions suggest that curare-induced channel openings occur during less than 1% of acetylcholine receptor – curare binding episodes. The outcome is (a) an agonist action too feeble to perturb the membrane voltage and (b) a powerful competitive antagonist action.Key words: curare, acetylcholine receptor, single channels, skeletal muscle.
A direct role of endogenous prostaglandins in reperfusion-induced cardiac arrhythmias
Authors: Moffat Margaret P. , Ferrier Gregory R. , Karmazyn Morris
Published: April 2011

The possible role of prostaglandins (PG) in arrhythmias associated with ischemia and reperfusion was studied in isolated, superfused canine Purkinje tissues. Ischemic conditions caused partial depolarization and decrease of excitability. Neither inhibition of PG synthesis (ibuprofen, 30 μg/mL) nor addition of exogenous PGF2α (1 ng/mL) modified responses to "ischemia." Reperfusion with normal Tyrode's solution stimulated PG production (measured as 6-keto-PGF1α) and induced a series of electrophysiological events. Under control conditions, Purkinje fibres rapidly repolarized. Subsequently, these tissues began to depolarize and oscillatory afterpotentials appeared. Purkinje tissues depolarized further and became temporarily inexcitable. Return of activity was associated with depolarization-induced automaticity. Ibuprofen prevented reperfusion-stimulated PG release. Ibuprofen also increased the magnitude of early repolarization and greatly attenuated subsequent depolarization. Depolarization-induced automaticity was not observed under these conditions; however, oscillatory afterpotentials were not abolished by ibuprofen. Addition of PGF2α to "ischemic" and reperfusion solutions in the presence of ibuprofen restored the arrhythmogenic responses. We conclude that release of endogenous prostaglandins contributes to electrophysiological changes elicited by reperfusion in canine Purkinje fibres.Key words: arrhythmias, ischemia, reperfusion, ibuprofen, prostaglandins.
The mechanism of the rate-dependent changes of the conducted action potential in rabbit ventricle
Authors: Ruiz-Petrich Elena , Leblanc Normand
Published: April 2011

Blockers of the transient outward current (4-aminopyridine) and the Ca current (Co2+) as well as injection of polarizing current during the plateau were used to assess the role of these current systems as determinants of action potential duration at different pacing rates. Papillary muscles and ventricular trabecula were superfused with oxygenated Krebs solution at 33 °C and driven at a basic rate of 1 Hz. The effects of varying the frequency of stimulation between 0.1 and 4 Hz on action potential parameters were determined under control conditions and during exposure to 2 mM 4-aminopyridine, 1–3 mM CoCl2, or a mixture of 4-aminopyridine and CoCl2. The control relationship between action potential duration and pacing rate showed a maximum between 1 and 2 Hz. Under 4-aminopyridine, the plateau height and the action potential duration increased. The rate-dependent shortening of the action potential at frequencies below 1 Hz was reduced or abolished, and enhanced shortening was observed at rates above 1 Hz. Exposure to Co2+ reduced the action potential shortening at rates higher than 1 Hz. Both blockers, 4-aminopyridine and Co2+ were necessary to eliminate the rate-dependent changes of the action potential duration. Our results indicated that both the transient outward current and the inward calcium current determine the plateau height and duration for frequencies ≤2 Hz, whereas at higher rates, the Ca current plays a dominant role.Key words: action potential duration, stimulation rate, Ca current, transient outward current.