Biomedical subjects

E D'Angelo

Publications and source records attributed to E D'Angelo.

At least 37 records · Page 2Linked to original sources

PubMed1998

Ionic mechanism of electroresponsiveness in cerebellar granule cells implicates the action of a persistent sodium current.

Although substantial knowledge has been accumulated on cerebellar granule cell voltage-dependent currents, their role in regulating electroresponsiveness has remained speculative. In this paper, we have used patch-clamp recording techniques in acute slice preparations to investigate the ionic basis of electroresponsiveness of rat cerebellar granule cells at a mature developmental stage. The granule cell generated a Na+-dependent spike discharge resistant to voltage and time inactivation, showing a linear frequency increase with injected currents. Action potentials arose when subthreshold depolarizing potentials, which were driven by a persistent Na+ current, reached a critical threshold. The stability and linearity of the repetitive discharge was based on a complex mechanism involving a N-type Ca2+ current blocked by omega-CTx GVIA, and a Ca2+-dependent K+ current blocked by charibdotoxin and low tetraethylammonium (TEA; <1 mM); a voltage-dependent Ca2+-independent K+ current blocked by high TEA (>1 mM); and an A current blocked by 2 mM 4-aminopyridine. Weakening TEA-sensitive K+ currents switched the granule cell into a bursting mode sustained by the persistent Na+ current. A dynamic model is proposed in which the Na+ current-dependent action potential causes secondary Ca2+ current activation and feedback voltage- and Ca2+-dependent afterhyperpolarization. The afterhyperpolarization reprimes the channels inactivated in the spike, preventing adaptation and bursting and controlling the duration of the interspike interval and firing frequency. This result reveals complex dynamics behind repetitive spike discharge and suggests that a persistent Na+ current plays an important role in action potential initiation and in the regulation of mossy fiber-granule cells transmission.

2-Amino-5-phosphonovalerate↗

PubMed1997

Synaptic activation of Ca2+ action potentials in immature rat cerebellar granule cells in situ.

Although numerous Ca2+ channels have been identified in cerebellar granule cells, their role in regulating excitability remained unclear. We therefore investigated the excitable response in granule cells using whole cell patch-clamp recordings in acute rat cerebellar slices throughout the time of development (P4-P21, n = 183), with the aim of identifying the role of Ca2+ channels and their activation mechanism. After depolarizing current injection, 46% of granule cells showed Ca2+ action potentials, whereas repetitive Na+ spikes were observed in an increasing proportion of granule cells from P4 to P21. Because Ca2+ action potentials were no longer observed after P21, they characterized an immature granule cell functional stage. Ca2+ action potentials consisted of an intermediate-threshold spike (ITS) activating at -60/-50 mV and sensitive to voltage inactivation and of a high-threshold spike (HTS), activating at above -30 mV and resistant to voltage inactivation. Both ITS and HTS comprised transient and protracted Ca2+ channel-dependent depolarizations. The Ca2+ action potentials could be activated synaptically by excitatory postsynaptic potentials, which were significantly slower and had a proportionately greater N-methyl-D-aspartate (NMDA) receptor-mediated component than those recorded in cells with fast repetitive Na+ spikes. The NMDA receptor current, by providing a sustained and regenerative current injection, was critical for activating the ITS, which was not self-regenerative. Moreover, NMDA receptors determined temporal summation of impulses during repetitive mossy fiber transmission, raising membrane potential into the range required for generating protracted Ca2+ channel-dependent depolarizations. The nature of Ca2+ action potentials was considered further using selective ion channel blockers. N-, L-, and P-type Ca2+ channels generated protracted depolarizations, whereas the ITS and HTS transient phase was generated by putative R-type channels (R(ITS) and R(HTS), respectively). R(HTS) channels had a higher activation threshold and were more resistant to voltage inactivation than R(ITS) channels. At a mature stage, most of the Ca2+-dependent effects depended on the N-type current, which promoted spike repolarization and regulated the Na+-dependent discharge frequency. These observations relate Ca2+ channel types with specific neuronal excitable properties and developmental states in situ. Synaptic NMDA receptor-dependent activation of Ca2+ action potentials provides a sophisticated mechanism for Ca2+ signaling, which might be involved in granule cell development and plasticity.

Action Potentials↗

PubMed1997

Lung and chest wall mechanics in patients with acquired immunodeficiency syndrome and severe Pneumocystis carinii pneumonia.

The aim of this study was to assess the mechanical characteristics of the respiratory system in patients with acquired immune deficiency syndrome (AIDS) and acute respiratory distress syndrome (ARDS) caused by Pneumocystis carinii pneumonia (PCP). In 12 mechanically ventilated patients, total respiratory system mechanics was assessed using the technique of rapid airway occlusion during constant flow inflation, and was partitioned into lung and chest wall components using the oesophageal balloon technique. We measured interrupter resistance (Rint), which mainly reflects airway resistance, additional resistance (deltaR) due to viscoelastic behaviour and time constant inequalities, and static elastance (Est). In addition, the static inflation volume-pressure (V-P) curve was assessed. In eight patients, computed tomography scans were performed within 2 days of the assessment of respiratory mechanics. Compared to values reported in the literature for normal subjects, Est and deltaR were markedly increased in AIDS patients with PCP, whilst Rint exhibited a relatively smaller increase. These changes, which involved only the lung and airways, were mainly due to the reduction of ventilated lung units, but additional factors were involved to cause independent modifications of lung stiffness, airway calibre, and viscoelastic properties. The changes in Rint, deltaR, and Est were similar to those observed in other studies on patients with ARDS of different aetiologies. At variance with common observations in the latter patients, none of the AIDS patients with PCP exhibited an inflection point on the static inflation V-P curve, suggesting little or no alveolar recruitment during lung inflation. This finding could be related to the distinctive histopathology of Pneumocystis carinii pneumonia. Indeed, computed tomography revealed homogeneous diffuse interstitial and alveolar infiltration rather than the dense, dependent opacities observed in other studies on acute respiratory distress syndrome of different aetiologies.

AIDS-Related Opportunistic Infections↗

PubMed1997

[Forced expiration. Various current concepts, 50 years after Robert Tiffeneau].

One hundred and fifty years after the original description of spirometry by Hutchinson and 50 years after the definition of his famous ratio by Tiffeneau, a certain number of physiological advances have enabled a better understanding of the determinants of the forced expired manoeuvre and to mitigate some of its inconveniences. This review focuses on three of these advances. The first is the influence of an inspiratory manoeuvre which precedes a forced expiration, on the expiratory flow. This influence is probably a consequence of viscoelastic phenomena and impose some strains on standardisation in current practice. The second is the possibility of detecting in a reproducible and simple fashion, without the need for co-operation on the part of the subject, a limitation in expiratory flow by the application of a negative expiratory pressure at the opening of the airways (NEP for negative expiratory pressure). The third is the possibility to verify in a simple fashion the quality of the expiratory performance achieved by the patient and thus to detect an insufficient effort in the force of a falling expiratory flow.

Dyspnea↗

PubMed1996

Insertional action of the abdominal muscles in rabbits and dogs.

The insertional action of the abdominal muscles was studied in supine anesthetized, apneic rabbits and dogs by comparing the changes in esophageal pressure (Pes), upper and lower rib cage circumference (Cru,u and Crc,I) and lung volume (VL) in response to electrical stimulation of all abdominal muscles before and after evisceration. In eviscerated animals, abdominal muscle contraction increased Pes and decreased both VL and Cre,I, but had no effect on Crc,u. Maximal responses were obtained at submaximal intensities of stimulation, and became larger with increasing lung volume. Relative to the vital capacity in intact animals, maximal delta VL for stimulation performed at FRC and TLC were 7.2 +/- 2.9(SD) and 39.5 +/- 7% in rabbits, and 6.3 +/- 0.8 and 18.3 +/- 5.9% in dogs, respectively. Relative to the changes in lung volume occurring with maximal contraction of the abdominal muscles in intact animals, the values of delta VL observed in the eviscerated animals amounted to approximately 35 and approximately 45% for stimulation performed at FRC and TLC, respectively. Hence, abdominal muscles exert substantial insertional action on the lower rib cage that can result in appreciable lung deflationary effects, particularly at elevated lung volumes.

Abdominal Muscles↗

PubMed1996

Differential long-lasting potentiation of the NMDA and non-NMDA synaptic currents induced by metabotropic and NMDA receptor coactivation in cerebellar granule cells.

UNLABELLED: Whole-cell patch-clamp recordings in rat cerebellar slices were used to investigate the effect of metabotropic glutamate receptor activation on mossy fibre-granule cell synaptic transmission. Transient application of 20 microM 1S, 3R-aminocyclopentane-1, 3-dicarboxylic acid simultaneously with low-frequency NMDA receptor activation induced long-lasting non-decremental potentiation of both NMDA and non-NMDA receptor-mediated synaptic transmission. Potentiation could be prevented by application of the metabotropic glutamate receptor antagonist (+)-O-methyl-4-carboxyphenyl-glycine at 500 microM. Characteristically, NMDA potentiation was two to three times as large as non-NMDA current potentiation, occurred only in a slow subcomponent, and was voltage-independent. This result demonstrates a pivotal role of NMDA receptors in the metabotropic potentiation of transmission, which may be important in regulating cerebellar information processing. KEYWORDS: cerebellum, LTP, metabotropic receptors, NMDA receptors, patch-clamp, rat

Animals↗

PubMed1996

Effects of bronchomotor tone and gas density on time dependence of forced expiratory vital capacity maneuver.

It has been shown that in normal subjects and chronic obstructive pulmonary disease (COPD) patients the maximal expiratory flows and FEV1 are significantly higher if the FVC maneuver is preceded by a rapid inspiration without an end-inspiratory pause (maneuver 1) compared with a slow inspiration with an end-inspiratory pause of approximately 5 s (maneuver 2). This time dependency of FVC was attributed primarily to loss of lung recoil (stress relaxation) during breath-holding at TLC, in association with time constant inequality within the lungs, and changes in bronchomotor tone. To examine the role of bronchomotor tone on time dependency of FVC, 11 COPD and 10 asthmatic patients performed FVC maneuvers 1 and 2 before and after administration of a bronchodilator drug (salbutamol). In addition, using the same approach, the effects of changing airway resistance per se were assessed in another group of 10 COPD patients and 10 normal subjects, while breathing air and after equilibration with 80% helium in oxygen. Main findings were: peak expiratory flow (PEF), FEV1, and maximal midexpiratory flow rate (MMF) were significantly larger with maneuver 1 than 2; after salbutamol administration and during helium-oxygen breathing, all indices increased significantly with both maneuvers but the relative differences between maneuvers 1 and 2 were unchanged. We conclude that time dependency of maximal expiratory flow-volume (MEFV) curves, as indexed by PEF, FEV1, and MMF, is largely independent of bronchomotor tone and gas density, and probably reflects mainly stress relaxation of the respiratory tissues. The relevance of time dependency of FVC maneuver in the assessment of bronchodilator response and density dependence is discussed.

Adult↗

PubMed1995

Miniature endplate current kinetics at the mouse neuromuscular junction: effects of temperature and medium viscosity.

The time course of miniature endplate currents (MEPCs), derived by extracellular focal recording, was studied in the mouse neuromuscular junction at different temperatures and medium viscosities, and in eserine-treated endplates. At low temperatures (6-10 degrees C), almost the whole MEPC decay is exponential and the rising phase is not significantly modified by the channel closing process. At physiological temperatures (38-40 degrees C), the early part of the decay is much slower than the later part and the rising phase is made shorter and smaller by channel closing, showing that the channel opening and channel closing processes overlap remarkably. Even at physiological temperatures, however, the late part of the MEPC decay shows an exponential time course. At high temperatures the channel opening process has low temperature sensitivity and slows down when bath solution viscosity is increased, suggesting that at high temperatures channel opening kinetics may mainly be controlled by the time course of acetylcholine diffusion. The lower limit of conformational change rate leading to channel opening was estimated at 10 degrees C (4400 s-1). Experimentally recorded MEPCs were mathematically simulated to obtain a quantitative description of the processes controlling MEPC generation. Mathematical simulation further suggests that (i) acetylcholine diffusion kinetics may affect the onset rate of MEPCs without, however, being rate-limiting; and (ii) partial, transient acetylcholinesterase inhibition operated by acetylcholine may explain the low temperature sensitivity exhibited by the onset rate of MEPCs at high temperatures.

Acetylcholine↗

PubMed1995

Synaptic excitation of individual rat cerebellar granule cells in situ: evidence for the role of NMDA receptors.

1. Current-clamp recordings were made in whole-cell patch-clamp configuration from ninety-one granule cells in parasagittal cerebellar slices obtained from 21- to 31-day-old rats. Recordings were performed at 30 degrees C. 2. Resting membrane potential was -58 +/- 6 mV (n = 43). The membrane voltage response to step current injection showed inward rectification consistent with increasing input resistance during membrane depolarization. Over -35 +/- 7 mV (n = 14) repetitive firing with little or no adaptation was activated. Spike frequency increased nearly linearly with injected current. 3. Unitary EPSPs obtained by stimulating the mossy fibre bundle had an amplitude of 11.4 +/- 2.1 mV (n = 22, holding potential = -75 mV). Synchronous activation of greater than one to two mossy fibres was needed to elicit action potentials. Antidromic stimulation elicited antidromic spikes and also EPSPs, presumably through a mossy fibre 'axon reflex'. 4. EPSPs were brought about by NMDA and non-NMDA receptor activation, accounting for about 70 and 30%, respectively, of peak amplitude at the holding potential of -70 mV. The EPSP decay conformed to passive membrane discharge after blocking the NMDA receptors. 5. No appreciable correlation was found between the time-to-peak and decay time constant of the EPSPs, consistent with the compact electrotonic structure of these neurons. 6. During membrane depolarization EPSP amplitude increased transiently, due to both a voltage-dependent increase of the NMDA component and inward rectification. In addition, EPSPs slowed down due to a slowdown of the NMDA component. 7. Temporal summation during high-frequency stimulation was sustained by NMDA receptors, whose contribution to depolarization tended to prevail over that of non-NMDA receptors during the trains. A block of the NMDA receptors resulted in reduced depolarization and output spike frequency. 8. This study, as well as extending previous knowledge to the intracellular level in vivo, provides evidence for a primary role of NMDA receptors in determining mossy fibre excitation of granule cells. It is suggested that the marked voltage dependence of the EPSP time course, which was mainly caused by voltage dependence in NMDA conductance, promotes the NMDA receptor-dependent enhancement of granule cell coding observed during repetitive mossy fibre activity.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1994

Voltage-dependent kinetics of N-methyl-D-aspartate synaptic currents in rat cerebellar granule cells.

Decay kinetics of N-methyl-D-aspartate excitatory postsynaptic currents (NMDA-EPSCs) have been voltage-dependent in some, but not all neurons studied so far, and almost no information has been available on the voltage-dependence of the rising phase. In this work we investigated the effect of membrane potential on rising and decay kinetics of the NMDA-EPSC in cerebellar granule cells using the tight-seal whole-cell recording technique. NMDA-EPSCs were evoked by electrical mossy fibre stimulation in the presence of 10 microM 6-cyano-7-nitroquinoxaline-2,3-dione, 1.2 mM Mg2+ and 5 microM glycine. The rate of rise of NMDA-EPSCs remained substantially unchanged when the cell was depolarized, indicating that the limiting step of channel opening was voltage-insensitive. The NMDA-EPSC, however, flattened around the peak and the time-to-peak increased. This observation was explained by the influence of decay. Decay was biphasic and slowed down with membrane depolarization. Moreover, the fast component of decay increased less than the slow component. This complex voltage-dependence may extend the integrative role of the NMDA current during synaptic transmission.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1994

Age-dependent expression of high-voltage activated calcium currents during cerebellar granule cell development in situ.

Ca2+ currents play a crucial role during neuronal growth. In this paper we describe the development of Ca2+ currents using whole-cell patch-clamp recordings in granule cells of cerebellar slices obtained from 7- to 24-day-old rats. Granule cells expressed high-voltage-activated (HVA) Ca2+ currents in different proportions. The percentage of cells with a measurable HVA current, and the size of HVA current increased in parallel with granule cell maturation. At less than 14 days HVA currents consisted of a fast- and slow-inactivating component, while at more than 19 days only the slow-inactivating component remained. The fast-inactivating component had faster activation and inactivation kinetics, a more negative threshold for activation, and steeper steady-state inactivation than the slow-inactivating component. Nifedipine (5 microM) partially blocked both components. omega-Conotoxin (5 microM, omega-CgTx) blocked the slow-inactivating component rather selectively. These results indicate that HVA currents change their gating and pharmacological properties during development. Although the mechanism at the molecular level remains speculative, the developmental changes of the HVA current are relevant to the processes of granule cell maturation and excitability.

Aging↗

PubMed1994

Mechanics of the abdominal muscles in rabbits and dogs.

In anesthetized, apneic rabbits and dogs, direct tetanic stimulations of the abdominal muscles (AMS) were performed at different tracheal pressures (Ptr) in the supine and upright posture. Lung volume (V), esophageal (Pes) and abdominal pressure (Pab), circumference of the upper and lower lung apposed rib cage (Crc, u and Crc, l) and of the abdomen (Cab), and transverse diameter of the rib cage facing the abdominal contents (Drc,ab) were measured. At Ptr = 0, Pab and Pes increased, and V decreased with increasing the strength of AMS; delta Pes and delta V eventually levelled off, while delta Pab was still increasing. Both delta Pes and delta V were larger in the upright posture, whereas delta Pab were similar. Relative to the expiratory reserve volume (ERV), maximal delta V in the supine and upright posture were 75.6 +/- 2.1 (mean +/- SE) and 86.1 +/- 2.2% in rabbits, and 56.5 +/- 3.4 and 75.2 +/- 3.7% in dogs. Maximal AMS decreased V and increased delta Pab the more so the larger the lung volume. In the volume range 10-70% VC, delta V were 3-4% VC larger in the upright posture, while delta Pab were similar in both postures. With AMS, Cab decreased, and Crc,u and Crc,l increased, while Drc,ab increased in dogs and decreased in rabbits. Hence, (a) the abdominal muscles can account for most of the ERV, particularly in the upright posture; (b) their maximal deflationary effects on the lung are already reached with submaximal activation; (c) their expiratory capacity is hindered by the expansion of the lung apposed rib cage and limited by diaphragmatic passive tension, and (d) their efficiency is reduced by paradoxical motion and distortion both between and within the lung apposed rib cage and abdominal compartments. Possible mechanisms for the dependency of delta V on species, volume and posture are discussed.

Abdominal Muscles↗

PubMed1994

The relationship between synaptogenesis and expression of voltage-dependent currents in cerebellar granule cells in situ.

In this work we consider the ontogenetic changes of membrane currents and their relationship with synaptogenesis in cerebellar granule cells. Recordings were performed in whole-cell patch-clamp configuration from cerebellar slices obtained from 4 to 31-day-old rats. Granule cells in the external granular layer, and non-connected granule cells in the internal granular layer expressed outward currents, and inconstantly also small Ca2+ currents, but no fast Na+ currents. Most connected granule cells expressed Ca2+ and Na+ currents. These data indicate that Ca2+ and Na+ current development occurs after synapse formation, while outward (K+) currents begin their development before. Mixed NMDA/non-NMDA synaptic currents were observed at all stages, while synaptic currents with a prominent NMDA component were observed exclusively at immature stages. At P4, ie 1-2 days after the arrival of the first granule cells in the internal granular layer, some granule cells already expressed mature synaptic and voltage-dependent currents, suggesting that establishment of mossy fibre synapses and development of membrane properties takes just 1-2 days to complete. Starting at P4, the probability of activating mossy fibre currents, and sizeable Ca2+ and Na+ currents increased at a similar rate, attaining a plateau level around P20. Average amplitude of Na+ and outward currents decreased until P10 and then increased attaining plateau soon beyond P20. Average amplitude of Ca2+ currents increased monotonically. The time courses of probability and average current amplitude curves are likely explained by changes in the rate of accumulation of migrating granule cells in the internal granular layer, and by changes in granule cell membrane surface extension. These data suggest a relevant role for the process of synapse formation in inducing the expression of new channels in the developing granule cells, which may involve Ca2+ influx through the NMDA channel.

Animals↗

PubMed1994

Chest wall interrupter resistance in anesthetized paralyzed humans.

Tracheal (Ptr) and esophageal (Pes) pressure and flow were measured in 12 supine anesthetized paralyzed normal subjects aged 16-22 yr. The subjects were ventilated with a fixed inflation volume (range 0.57-0.62 liter) and with different constant flows ranging between 0.24 and 1.12 l/s. A rapid airway shutter (closing time 10-15 ms) was used to briefly occlude (0.4-0.9) the airways at end inspiration for 33-44 consecutive breaths. At each flow level, Ptr and Pes records obtained during end-inspiratory occlusions were ensemble averaged to allow for the cardiac artifacts. The interrupter resistances of the chest wall and respiratory system were assessed as the rapid fall in Pes and Ptr with occlusion divided by the flow preceding the occlusion. Interrupter resistances of both the chest wall and lung were independent of flow and averaged 0.4 +/- 0.1 and 1.5 +/- 0.4 (SD) cmH2O.s.l-1, respectively. The contribution of the chest wall to the total interrupter resistance was approximately 27% at flows < or = 1 l/s.

Adolescent↗

PubMed1994

Dependence of maximal flow-volume curves on time course of preceding inspiration in patients with chronic obstruction pulmonary disease.

Thirteen patients with chronic obstructive pulmonary disease (COPD) performed forced vital capacity (FVC) maneuvers either immediately after a rapid inspiration (maneuver 1) or after a slow inspiration with a 4- to 6-s end-inspiratory pause (maneuver 2). Seated in a body plethysmograph, they breathed through a pneumotachograph. Inspirations were initiated from resting end-expiratory lung volume. Abdominal muscle activity was recorded by means of surface electrodes. With maneuver 1: (1) expiratory flows were 20 to 40% larger in the volume range 10 to 95% FVC; (2) peak expiratory flow was on average 30% higher; and (3) FEV1, expressed as percent of FVC, increased by about 8%. No substantial differences in the pattern of abdominal muscle activity occurred between maneuvers. The dependence of maximal flow-volume curves on the time course of the preceding inspiration is probably related in part to the viscoelastic elements present within the respiratory system, which, stretched during rapid inspirations, increase the effective elastic recoil during the FVC maneuver 1. This cannot occur with maneuver 2, because of stress relaxation of the viscoelastic elements during the 4- to 6-s breathhold preceding the FVC maneuver. Other factors (e.g., time constant inequality) might also be involved. In any case, the results imply that the inspiratory maneuver prior to FVC must be standardized.

Abdominal Muscles↗

PubMed1994

[Effect of the chronic treatment with L-acetylcarnitine in Down's syndrome].

Neuropsychologic tests were performed in subjects with Down syndrome in order to assess the effect of a 90-day treatment with L-acetyl-carnitine (LAC). Findings were evaluated statistically (Wilcoxon test) and compared to three further groups of subjects: untreated Down syndrome, mental deficiency due to other cases treated and not treated with LAC (Mann-Whitney U-test). Treated Down syndrome patients showed statistically significant improvements of visual memory and attention both in absolute terms and in comparison with the other groups. No improvement was found in mentally deficient non-Down subjects, so that the favourable effect of LAC appears to be specific for Down patients. In view of the analogies of the pathology and neurochemistry between Down syndrome and Alzheimer degenerative deficiency (deficit of cholinergic transmission) it is suggested that the action of LAC in these pathologies is related to its direct and indirect cholinomimetic effect.

Acetylcarnitine↗

PubMed1993

Different proportions of N-methyl-D-aspartate and non-N-methyl-D-aspartate receptor currents at the mossy fibre-granule cell synapse of developing rat cerebellum.

The mossy fibre-granule cell synapse undergoes major developmental changes during the second and third weeks after birth. We investigated synaptic transmission during postnatal days 10-22 by means of whole-cell patch-clamp recordings from granule cells in situ. Parasagittal slices were cut from rat cerebellar vermis, and excitatory postsynaptic currents were evoked in granule cells by mossy fibre stimulation with 1.2 mM Mg++ in the extracellular solution. In the majority of granule cells recorded at postnatal days 16-22, excitatory currents were characterized by a fast initial peak followed by a slower component, while in many of the cells recorded at more immature stages, the fast peak was virtually absent. Pharmacological and kinetic data indicated that the fast and slow components were mediated by non-N-methyl-D-aspartate and N-methyl-D-aspartate receptor activation, respectively. The magnitude of the non-N-methyl-D-aspartate current increased with developmental age, while the magnitude of the NMDA current did not change markedly. The age-dependent change of the non-N-methyl-D-aspartate currents could not be accounted for by changes in recording conditions or granule cell electrotonic properties. Furthermore, from postnatal day 11 to 16 the extent of Mg++ block on the N-methyl-D-aspartate receptor did not change, and could not explain the increasing non-N-methyl-D-aspartate/N-methyl-D-aspartate current ratio. We concluded therefore that the age-dependent increase of the non-N-methyl-D-aspartate current was the main cause of the different postsynaptic current waveforms observed at different ages. The developmental change in the proportion of N-methyl-D-aspartate and non-N-methyl-D-aspartate currents may be relevant to the processes regulating granule cell maturation and excitability.

2-Amino-5-phosphonovalerate↗

PubMed1993

Dependence of maximal flow-volume curves on time course of preceding inspiration.

Thirteen normal subjects, sitting in a body plethysmograph and breathing through a pneumotachograph, performed forced vital capacity maneuvers after a rapid inspiration without or with an end-inspiratory pause (maneuvers 1 and 2) and after a slow inspiration without or with an end-inspiratory pause (maneuvers 3 and 4), the pause lasting 4-6 s. Inspirations were initiated close to functional residual capacity. At all lung volumes, expiratory flow was larger with maneuver 1 than with any other maneuver and, over the upper volume range, larger with maneuver 3 than with maneuver 4, whereas it was similar for maneuvers 2 and 4. Relative to corresponding values with maneuver 4, peak expiratory flow was approximately 16 and approximately 4% larger with maneuvers 1 and 3, respectively, whereas forced expiratory volume in 1 s increased by approximately 5% only with maneuver 1. The time dependence of maximal flow-volume curves is consistent with the presence of viscoelastic elements within the respiratory system (D'Angelo et al. J. Appl. Physiol. 70: 2602-2610, 1991).

Adult↗