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S A Bloomfield

Publications and source records attributed to S A Bloomfield.

At least 37 records · Page 2Linked to original sources

Estradiol effect on anterior crural muscles-tibial bone relationship and susceptibility to injury.

The study's objective was to determine whether estradiol (E2) deficiency alters the functional relationship of muscle to bone and causes a differential increase in injury susceptibility. Ovariectomized 6-wk-old mice were administered E2 (40 micrograms. day-1. kg-1; n = 8) or the oil vehicle (n = 8) for 21 days. The anterior crural muscles of the left hindlimb were then stimulated to produce 150 maximal in vivo eccentric contractions. In vitro functional measurements were then made on the extensor digitorum longus (EDL) muscle and tibia from both the exercised and unexercised legs. The maximal isometric torque produced by the anterior crural muscles before the eccentric contraction protocol and the unexercised EDL maximal isometric tetanic force (P(0)) were higher in E2-treated mice by 18 and 14%, respectively (P < or = 0.03). Both ultimate load and stiffness for the unexercised tibia were higher by 16% in E2-treated mice (P < or = 0.03). The muscle-to-bone relationship of these measurements was unaffected by E2 status (P > or = 0.59). No evidence for increased injury susceptibility was found in either tissue from E2-deficient mice. In fact, the decrement in P(0) was only 36.9 +/- 3.8% in exercised EDL muscles from E2-deficient mice compared with 50.6 +/- 4.2% in exercised muscles from E2-treated mice (P = 0.03). Tibia stiffness was 3.9% higher in bones from exercised legs than in bones from unexercised legs (72.64 +/- 2.77 vs. 69.95 +/- 2.66 N/mm; P = 0.05) with ultimate load showing a similar trend (P = 0.07); no effect of E2 status was observed on these differences (P > or = 0.53). In conclusion, the functional relationship of bone to muscle and the susceptibility to injury in bone are not altered by the presence of E2 in ovariectomized mice; however, E2 does increase injury susceptibility in the EDL muscle.

Animals↗

Effect of spike blockade on the receptive-field size of amacrine and ganglion cells in the rabbit retina.

1. Intracellular recordings were obtained from 21 amacrine cells and 12 ganglion cells in the isolated, superfused retina-eyecup of the rabbit. Cells were subsequently labeled with horseradish peroxidase (HRP) or N-(2-aminoethyl)-biotinamide hydrochloride (Neurobiotin) for morphologic identification. 2. Initial experiments performed on three amacrine cells and three ganglion cells showed that 1 microM tetrodotoxin (TTX) abolished all spiking. This included both large-amplitude and small-amplitude spikes recorded in many amacrine cells, indicating that they are mediated by voltage-gated sodium channels. 3. The center-receptive-field size of 18 amacrine cells and 9 ganglion cells was measured with the use of a 50-microns-wide/6.0-mm-long rectangular slit of light that was displaced along its minor axis (parallel to the visual streak) in steps as small as 3 microns. The retina was then bathed in 1 microM TTX, or individual cells were injected with 50 mM QX-314, a quatemary lidocaine derivative, to abolish all spiking, and the center-receptive field of each cell was then remeasured. 4. Although TTX blocked spiking in all ganglion cells (dendritic diameters ranging from 302 to 969 microns), it produced no significant change in the size of their center-receptive fields. This finding argues that passive, electrotonic spread of synaptic inputs to ganglion cell dendritic arbors is adequate for efficient propagation from terminal branches to the soma; active propagation via voltage-gated sodium channels plays no apparent role. 5. In contrast, TTX and QX-314 had variable effect on the receptive fields of amacrine cells, which was related to the size of their dendritic arbors. Whereas TTX had no significant effect on the receptive-field size of amacrine cells whose dendritic arbors were < 525 microns across, the center-receptive fields of larger amacrine cells were reduced, on average, by 40%; QX-314 produced a very similar average reduction of 39%. Moreover, for these larger cells, there was a direct relationship between the magnitude of the reduction in receptive-field size produced by TTX or QX-314 and the size of a cell's dendritic arbor. This relationship was true whether the change in receptive-field size was measured in absolute terms or as percent reduction from control values. 6. Interestingly, TTX and QX-314 also significantly reduced the amplitude of slow potentials recorded in amacrine cells by an average of 22 and 24%, respectively. However, the amplitude of slow potentials recorded in ganglion cells were relatively uneffected by TTX. 7. These findings are consistent with the idea that, for amacrine cells with dendritic arbors spanning > 525 microns, active propagation of synaptic signals mediated by voltage-gated sodium channels is necessary for efficient movement of information across a cell's dendritic arbor and thus plays a major role in shaping their receptive fields. Although the TTX effects may also reflect an indirect contribution from altered synaptic input derived from presynaptic spiking neurons, the strong similarity between the effects of TTX and QX-314 argues that any such contribution was minor. For smaller amacrine cells, passive, electrotonic spread of signals appears adequate for efficient propagation within their limited dendritic arbors.

Anesthetics, Local↗

Orientation-sensitive amacrine and ganglion cells in the rabbit retina.

1. Intracellular recordings were obtained from amacrine and ganglion cells in the isolated, superfused retina-eyecup preparation of the rabbit to test the orientation sensitivity of their responses. Cell identification was based on morphological criteria following injection of horseradish peroxidase (HRP) or N-(2-aminoethyl)-biotinamide hydrochloride (Neurobiotin) to visualize soma-dendritic architectures. 2. In terms of the physiological mechanisms generating their sensitivity, two types of orientation-sensitive amacrine cell and a single type of orientation-sensitive ganglion cell were found. These cell types were termed orientation selective and orientation biased. Cells were subtypes further into on- or off-center receptive-field categories. 3. The receptive fields of orientation-selective amacrine and ganglion cells were composed of two inhibitory fields that flanked the excitatory center receptive field along the preferred orientation. These inhibitory flanks produced a center receptive-field anisotropy with its major axis corresponding to the preferred orientation: either parallel or orthogonal to the visual streak. When a stimulus was oriented orthogonal to the preferred orientation (i.e., at the null orientation), the inhibitory fields were stimulated, resulting in a null inhibition that blocked the center-mediated excitation. Stimulation of these inhibitory flanks was absolutely essential to evoke the orientation selectivity of these cells. The null response reflected inhibition associated with a conductance increase and not disfacilitation. 4. Orientation-biased amacrine cells displayed a center receptive-field anisotropy with its major axis oriented either parallel or orthogonal to the visual streak. These cells preferred light stimuli oriented along the major axis of the center receptive field. However, whereas the excitatory response of these cells was reduced when a stimulus was rotated from the preferred orientation, there was no corresponding hyperpolarization. No null inhibition was detected even after modulation of the membrane potential with extrinsic current. 5. Although orientation-biased amacrine cells were morphologically heterogeneous, they all displayed dendritic arbors that were markedly elongated along an axis corresponding to their physiological preferred orientation. Thus it appears that the elongated dendritic fields of these cells may provide for the anisotropy of their center receptive fields and, in turn, their orientation sensitivity. 6. Orientation-selective amacrine cells formed a rather homogeneous morphological group of cells. These neurons displayed large, radially symmetric dendritic arbors with diameters averaging 1,100 microns. There were no asymmetries in their dendritic fields and thus no clear structural basis for their orientation selectivity. 7. In contrast, orientation-selective ganglion cells displayed diverse soma-dendritic architecture and thus could not be placed into a single morphological class.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Catecholamine response to exercise and training in individuals with spinal cord injury.

It is unknown whether the catecholamine (CAT) response to acute exercise and prolonged training in humans with spinal cord injury (SCI) is similar to that of neurologically intact man. Plasma samples were collected from seven subjects with chronic SCI (level of injury C5-T7) at rest and during voluntary arm-crank ergometry (ACE) before and after 6 months of training with functional electrical stimulation cycle ergometry (FES-CE). Similar plasma collections were made during one FES-CE exercise training session after 6 months of training. Norepinephrine (NE) and epinephrine (EPI) were measured by HPLC. After FES-CE training, resting NE decreased 37% (950 +/- 150 vs 1510 +/- 350 pmol.l-1 pretraining); resting EPI decreased 80% (54 +/- 10 vs 163 +/- 32 pmol.l-1 pretraining) (P < 0.05 by paired t-tests). No significant changes were observed in group means after training for the CAT response to submaximal ACE; however, five of seven subjects exhibited greater increments in plasma NE with ACE after FES-CE training. Acute FES-CE exercise elicited a 55-844% increase in NE, and a 35-350% increase in EPI above resting values with power outputs eliciting heart rates of 90-146 bpm. These data provide evidence for a systemic CAT response in subjects with SCI during acute FES-CE and reduced resting CAT following 6 months of training with FES-CE.

Adult↗

Non-weightbearing exercise may increase lumbar spine bone mineral density in healthy postmenopausal women.

Seven postmenopausal women exercised regularly at moderate intensities (60-80% of maximum heart rate) for eight months on bicycle ergometers. Evaluation of bone mineral density by dual photon absorptiometry revealed a significant (P < 0.01) + 3.55 +/- 1.43% (mean +/- SE) increase in lumbar spine density in the exercisers compared with the 2.44 +/- 0.81% decrease noted in seven sedentary controls. No significant difference in change in femoral neck density was noted between the two groups (+2.51 +/- 2.10% v -0.74 +/- 0.72% for exercisers and controls, respectively; P > 0.10). Dietary intake of calcium and vitamin D was similar in both groups, as was previous exposure to estrogen replacement therapy. These data provide evidence of a prospective nature that non-weightbearing exercise may be effective in reversing bone loss in healthy postmenopausal women.

Bicycling↗

A unique morphological subtype of horizontal cell in the rabbit retina with orientation-sensitive response properties.

Intracellular recordings were obtained from horizontal cells in the rabbit retina to assess the orientation sensitivity of their visual responses to moving and stationary rectangular slits of light. Cells were subsequently labeled with horseradish peroxidase (HRP) for morphological identification. The responses of A-type horizontal cells and those of the somatic and axon terminal endings of B-type horizontal cells (with the exception of one cell) were found to be insensitive to the orientation of light stimuli. However, 20 horizontal cells encountered within or just superior to the visual streak displayed clear orientation-sensitive response properties. These cells were divided into two groups: the majority (70%) showed preference for light stimuli oriented parallel to the visual streak, whereas the remainder preferred stimuli oriented orthogonal to the visual streak. Analysis of the shape of the receptive fields of these cells by means of a narrow, displaced slit of light revealed an anisotropy with the major or elongated axis of the receptive field of each cell aligned along the same angle as its physiological preferred orientation. Morphologically, the orientation-sensitive horizontal cells formed a homogeneous group with an architecture corresponding to that of elongated A-type or Ae-type horizontal cells reported previously in the rabbit retina. These cells showed a marked elongation of their dendritic arbors with the major axes oriented either parallel or orthogonal to the visual streak. Furthermore, the orientation of the dendritic arbor of each cell matched that of its physiological preferred orientation. The present results, then, suggest strongly that the orientation sensitivity of Ae-type horizontal cells results directly from the asymmetry in their dendritic arbors. The spatial location and specialized physiology of Ae-type horizontal cells suggest that they play a role in the formation of orientation-sensitive properties exhibited by more proximal neurons in the rabbit retina.

Animals↗

Effects of downhill running on the responses to an oral glucose challenge.

Because muscle damage from eccentric exercise has been associated with alterations in muscle glycogen metabolism, this study determined the effects of exercise on the insulin and glucose responses to an oral glucose tolerance test (OGTT). In a repeated-measures design, 11 subjects undertook either no exercise, 2 min of isokinetic leg exercise, or 50 min of level or downhill running. No exercise was performed and diet was controlled during the 48 hrs after the treatments and before the OGTT. Ratings of muscle soreness and CK activity were significantly elevated 48 hrs after downhill running. Level running also increased CK activity but did not induce muscle soreness. Isokinetic exercise did not affect either one. Blood glucose responses to the OGTT were similar among the treatments. In contrast, the insulin responses to the OGTT following downhill running were significantly increased. These results suggest that eccentric exercise associated with downhill running that results in delayed muscle soreness is associated with the development of a mild insulin-resistant condition.

Adult↗

Relationship between receptive and dendritic field size of amacrine cells in the rabbit retina.

1. Intracellular recordings were obtained from 40 amacrine cells in the isolated, superfused retina eyecup of the rabbit. Cells were subsequently labeled with horseradish peroxidase for morphological identification. Many of these cells displayed dendritic morphology consistent with that of amacrine cells described in prior anatomic studies, including starburst, A17, AII, and DAPI-3 cells. 2. The center receptive field of amacrine cells was measured with a 50- or 95-microns-wide, 6.0-mm-long rectangular slit of light that was displaced along its minor axis (parallel to the visual streak) in increments as small as 3 microns. The extent of the receptive field was calculated as the total distance over which the displaced slit could evoke a center response. Area summation of amacrine cells was measured with concentric spots of light with increasing diameters centered over the cell. 3. For a single amacrine cell, the receptive field size was comparable to the extent of its dendritic arbor. For the total population of amacrine cells, there was a strong, linear relationship between receptive field and dendritic field size. The receptive fields were, on average, 27% larger than the corresponding dendritic arbors, but this discrepancy can be accounted for entirely by tissue shrinkage associated with histological processing and a small imprecision of the light stimuli. Area summation measurements were consistent with those of receptive fields and were also related linearly to the dendritic field size of cells. 4. These findings indicate that even when the slit of light was placed at the distal edges of the dendritic arbor, synaptic inputs activated there were propagated effectively to the soma and recorded by microelectrodes placed there. In addition, amacrine cells were capable of summating synaptic inputs distributed throughout the entire arbor. 5. These results are inconsistent with the findings of prior computational modeling studies of passive, dendritic current flow in A17 and starburst amacrine cells that synaptic inputs on distal dendritic branches are isolated electrically from the soma and that these branches form autonomous, functional subunits. 6. The majority of amacrine cells encountered displayed light-evoked and/or spontaneous action potentials. These action potentials often took the form of high-amplitude somatic and low-amplitude dendritic spikes. On average, spiking amacrine cells showed considerably larger dendritic fields than nonspiking amacrine cells. In fact, all amacrine cells with arbors greater than 436 microns, which formed 45% of the total population, displayed spike activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Two types of orientation-sensitive responses of amacrine cells in the mammalian retina.

Neurons sensitive to the orientation of light stimuli exist throughout the mammalian visual system, suggesting that this spatial feature is a fundamental cue used by the brain to decipher visual information. The most peripheral neurons known to show orientation sensitivity are the retinal ganglion cells. Considerable morphological and pharmacological data suggest that the orientation sensitivity of ganglion cells is formed, at least partly, by the amacrine cells, which are laterally oriented interneurons presynaptic to the ganglion cells in the inner plexiform layer. So far there have been few studies of the responses of amacrine cells to oriented visual stimuli and their role in forming orientation-sensitive responses in the retina remains unclear. Here I report the novel finding of a population of amacrine cells in the rabbit retina which are orientation-sensitive. These amacrine cells can be divided into two subtypes, whose orientation sensitivity is manufactured by two distinct mechanisms. The orientation sensitivity of the first subtype of amacrine cell is formed from the interactions of excitatory, centre-receptive field synaptic inputs and inhibitory inputs of opposite polarity, whereas that for cells of the second subtype seems to be the product of a marked asymmetry in their dendritic arbors.

Animals↗

Dendritic arbors of large-field ganglion cells show scaled growth during expansion of the goldfish retina: a study of morphometric and electrotonic properties.

The retina of the goldfish grows by a balloon-like expansion and by the addition of new neurons at the margin. It has been proposed that as a consequence of this expansion the dendritic arbors of ganglion cells in central retina grow in a uniform manner without the addition of new branches. In the present study, we have examined this proposal by comparing the geometries of individual dendritic arbors of large-field ganglion cells from the retinas of small/young and large/old fish. These comparisons were based on measurements of several parameters of dendritic morphology, including number of segments and branches, branch angles, changes in diameter at branch points, and proximal versus distal distribution of arbor length. In addition, we used passive, steady-state cable modeling as an independent method of estimating the functional architectures of small and large dendritic arbors. Our morphometric data indicate that, though they are very different in absolute size, dendritic arbors of small and large ganglion cells have remarkably similar architectures. Analysis with steady-state cable equations indicates that the arbors from small and large cells have equivalent electrotonic lengths and show comparable propagation of synaptic currents. These data are consistent with the hypothesis that dendritic arbors of small and large ganglion cells are scaled versions of one another. We conclude that the growth of these cells during the expansion of the retina is the result of the addition of dendritic mass to an arbor whose basic geometry remains unchanged.

Animals↗

Dendritic current flow in relay cells and interneurons of the cat's lateral geniculate nucleus.

We used a passive, steady-state cable model to simulate current flow within the dendritic arbors of relay cells and interneurons in the cat's lateral geniculate nucleus. In confirmation of our previous work on relay cells, we found them to be electronically compact; thus a postsynaptic potential generated anywhere in a relay cell's dendritic arbor spreads with relatively little attenuation throughout the arbor and to its soma. An interneuron is very different. Its arbor is much more extensive electronically with the result that a postsynaptic potential significantly affects only local areas of the dendritic arbor, and only inputs to proximal dendrites or to the soma will much affect the soma. Since much of the interneuron's synaptic output derives from dendritic terminals that are both presynaptic and postsynaptic, its dendritic arbor may contain many local circuits that perform neuronal computations independently of each other, and this processing might be invisible to the soma. Furthermore, these interneurons possess conventional axonal outputs, and these contact postsynaptic profiles that are quite different from the postsynaptic targets of the dendritic terminals. Presumably, the axonal output reflects the integrated computations performed on proximal synaptic inputs, and it uses conventional action potentials to convey this output. We suggest that the interneuron does double duty: its dendritic arbor is used for many independent local circuits that perform one set of neuronal computations, and its axonal output represents conventional neuronal integration of proximal synaptic inputs.

Animals↗

Postsynaptic potentials recorded in neurons of the cat's lateral geniculate nucleus following electrical stimulation of the optic chiasm.

1. We recorded intracellularly from X and Y cells of the cat's lateral geniculate nucleus and measured the postsynaptic potentials (PSPs) evoked from electrical stimulation of the optic chiasm. We used an in vivo preparation and computer averaged the PSPs to enhance their signal-to-noise ratio. 2. The vast majority (46 of 50) of our sample of X and Y cells responded to stimulation of the optic chiasm with an excitatory postsynaptic potential (EPSP) followed by an inhibitory postsynaptic potential (IPSP); these were tentatively identified as relay cells. We quantified several parameters of these PSPs, including amplitude, latency, time to peak (i.e., rise time), and duration. 3. Among the relay cells, the latencies of both the EPSP and action potential evoked by optic chiasm stimulation were shorter in Y cells than in X cells. Furthermore, the difference between the latencies of the EPSP and action potential was shorter for Y cells than for X cells. This means that the EPSPs generated in Y cells reached threshold for generation of action potentials faster than did those in X cells. The EPSPs of Y cells also displayed larger amplitudes and faster rise times than did those in X cells, but neither of these distinctions was sufficient to explain the shorter latency difference between the EPSP and action potential for Y cells. 4. The EPSPs recorded in relay Y cells had longer durations than did those in relay X cells. Our data suggest that the subsequent IPSP actively terminates the EPSP, which, in turn, suggests that the time interval between EPSP and IPSP onsets is longer in Y cells than in X cells. Furthermore, we found that, for individual Y cells, the latency and duration of the evoked EPSP were inversely related. These observations lead to the conclusion that the latency of IPSPs activated from the optic chiasm is relatively constant among Y cells and thus independent of the EPSP latencies. Thus the excitation and inhibition produced in individual geniculate Y cells may originate from different populations of retinogeniculate axons. 5. The IPSPs recorded in geniculate relay cells following optic chiasm stimulation could be divided into three groups based on their durations. The majority of both X and Y cells showed short-duration IPSPs, whereas the remainder of Y cells displayed medium-duration IPSPs, and the remaining X cells displayed long-duration IPSPs. A positive correlation was seen between the time to peak and duration of these IPSPs.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Passive cable properties and morphological correlates of neurones in the lateral geniculate nucleus of the cat.

1. We used an in vivo preparation of the cat to study the passive cable properties of sixteen X and twelve Y cells in the lateral geniculate nucleus. Cells were modelled as equivalent cylinders according to Rall's formulations (Rall, 1959a, 1969, 1977). We injected intracellular current pulses into these geniculate neurones, and we analysed the resulting voltage transients to obtain the cable parameters of these cells. In addition, fifty-four physiologically characterized neurones were labelled with horseradish peroxidase (HRP) and analysed morphologically. 2. Analysis of HRP-labelled geniculate neurones showed that the dendritic branching pattern of these cells adheres closely to the 3/2 power rule. That is, at each branch point, the diameter of the parent branch raised to the 3/2 power equals the sum of the diameters of the daughter dendrites after each is raised to the 3/2 power. Furthermore, preliminary data indicate that the dendritic terminations emanating from each primary dendrite occur at the same electrotonic distance from the soma. These observations suggest that both X and Y cells meet the geometric constraints necessary for reduction of their dendritic arbors into equivalent cylinders. 3. We found a strong linear relationship between the diameter of each primary dendrite and the membrane surface area of the arbor emanating from it. We used this relationship to derive an algorithm for determining the total somatic and dendritic membrane surface area of an X and Y cell simply from knowledge of the diameters of its soma and primary dendrites. 4. Both geniculate X and Y cells display current-voltage relationships that were linear within +/- 20 mV of the resting membrane potential. This meant that we could easily remain within the linear voltage range during the voltage transient analyses. 5. X and Y cells clearly differ in terms of many of their electrical properties, including input resistance, membrane time constant and electrotonic length. The difference in input resistance between X and Y cells cannot be attributed solely to the smaller average size of X cells, but it also reflects a higher specific membrane resistance (Rm) of the X cells. Furthermore, X cells exhibit electrotonic lengths slightly larger than those of Y cells, but both neuronal types display electrotonic lengths of roughly 1. This indicates that even the most distally located innervation to these cells should have considerable influence on their somatic and axonal responses.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Effects of physical deconditioning after intense endurance training on left ventricular dimensions and stroke volume.

To determine the role of preload in maintaining the enhanced stroke volume of upright exercise-trained endurance athletes after deconditioning, six highly trained subjects undergoing upright and supine bicycle ergometry were characterized before and after 3, 8 and 12 weeks of inactivity that reduced oxygen uptake by 20%. During exercise, oxygen uptake, cardiac output by carbon dioxide rebreathing, cardiac dimensions by M-mode echocardiography, indirect arterial blood pressure and heart rate were studied simultaneously. Two months of inactivity resulted in a reduction in stroke volume, calculated as cardiac output/heart rate, during upright exercise (p less than 0.005) without a significant change during supine exercise. A concomitant decrease in the left ventricular end-diastolic dimension from the trained to the deconditioned state was observed in the upright posture (5.1 +/- 0.3 versus 4.6 +/- 0.3 cm; p = 0.02) but not with recumbency (5.4 +/- 0.2 versus 5.1 +/- 0.3 cm; p = NS). There was a strong correlation between left ventricular end-diastolic dimension and stroke volume (r greater than 0.80) in all subjects. No significant changes in percent fractional shortening or left ventricular end-systolic dimension occurred in either position after cessation of training. Estimated left ventricular mass was 20% lower after 3 and 8 weeks of inactivity than when the subjects were conditioned (p less than 0.05 for both). Thus, the endurance-trained state for upright exercise is associated with a greater stroke volume during upright exercise because of augmented preload. Despite many years of intense training, inactivity for only a few weeks results in loss of this adaptation in conjunction with regression of left ventricular hypertrophy.

Adult↗

A functional organization of ON and OFF pathways in the rabbit retina.

Intracellular electrophysiological recordings were obtained from amacrine and ganglion cells in an isolated, superfused retina-eyecup preparation of the rabbit. Cells were characterized physiologically, after which cell-staining was accomplished by intracellular iontophoresis of HRP. A computer-assisted image-processing system was used to study the dendritic stratification pattern of HRP-labeled neurons within the inner plexiform layer (IPL). Our results support the concept that the IPL is functionally divided into a distal OFF region and proximal ON layer. ON and OFF ganglion and amacrine cells show dendritic arborizations consistent with this division and ON-OFF ganglion cells have processes in both portions of the IPL. It appears that these functional subdivisions of the IPL reflect excitatory, but not necessarily inhibitory, inputs. Thus, the pattern of dendritic arborization of a cell appears to predict its physiological response polarity, regardless of the type of inhibition it receives.

Animals↗

Effects of detraining on responses to submaximal exercise.

Seven endurance-trained subjects were studied 12, 21, 56, and 84 days after cessation of training. Heart rate, ventilation, respiratory exchange ratio, and blood lactate concentration during submaximal exercise of the same absolute intensity increased (P less than 0.05) progressively during the first 56 days of detraining, after which a stabilization occurred. These changes paralleled a 40% decline (P less than 0.001) in mitochondrial enzyme activity levels and a 21% increase in total lactate dehydrogenase (LDH) activity (P less than 0.05) in trained skeletal muscle. After 84 days of detraining, the experimental subjects' muscle mitochondrial enzyme levels were still 50% above, and LDH activity was 22% below, sedentary control levels. The blood lactate threshold of the detrained subjects occurred at higher absolute and relative (i.e., 75 +/- 2% vs. 62 +/- 3% of maximal O2 uptake) exercise intensities in the subjects after 84 days of detraining than in untrained controls (P less than 0.05). Thus it appears that a portion of the adaptation to prolonged and intense endurance training that is responsible for the higher lactate threshold in the trained state persists for a long time (greater than 85 days) after training is stopped.

Blood Glucose↗

Roles of aspartate and glutamate in synaptic transmission in rabbit retina. I. Outer plexiform layer.

Intracellular recordings were obtained from horizontal and bipolar cells of the superfused, isolated retina-eyecup of the rabbit. The putative neurotransmitters aspartate, glutamate, and several analogues were added to the superfusate while the membrane potential and light-responsiveness of the retinal neurons were monitored. Both L-aspartate and L-glutamate mimicked the actions of the endogenous photoreceptor transmitter on horizontal cells, on-bipolar cells, and off-bipolar cells. At applied concentrations of 2.5-20 mM, the actions of L-aspartate and L-glutamate were indistinguishable. D-aspartate potentiated the effects of both L-aspartate and L-glutamate on horizontal cells. This suggests that active uptake systems for these amino acids exist in the outer plexiform layer (OPL) of the rabbit retina. The glutamate analogue kainate produced effects similar to those of aspartate and glutamate on second-order neurons, but at concentrations lower by over two orders of magnitude. The glutamate analogue quisqualate had effects similar to kainate but with much less potency. The aspartate analogue n-methyl DL-aspartate (NMDLA) antagonized the effects of the photoreceptor transmitter on horizontal and off-bipolar cells. This action of NMDLA was only observed at low concentrations (50 microM). In addition, NMDLA could block the effects of exogenously applied kainate. The NMDLA had no clear effects on on-bipolar cells. The glutamate analogue 2-amino-4-phosphonobutyrate reversibly blocked the responses of on-bipolar cells but had no effect on either horizontal or off-bipolar cell responses. This suggests that on-bipolar cells possess a unique synaptic receptor. The aspartate analogue 2-amino-3-phosphonoproprionate did not show this selectivity, suggesting that this unique receptor is a glutamate-preferring receptor. The antagonists alpha-methyl glutamate, alpha-amino adipate, and glutamate diethyl ester all showed only a weak ability to antagonize the actions of the photoreceptor transmitter on second-order neurons. The results of this study indicate that glutamate or a glutamate-like substance is the likely transmitter of rods and cones in the rabbit retina. A comparison of the present findings with those previously obtained in lower vertebrate retinas suggests that the basic pharmacological design of the OPL of all vertebrate retinas is very similar.

Animals↗

Roles of aspartate and glutamate in synaptic transmission in rabbit retina. II. Inner plexiform layer.

Intracellular recordings were obtained from amacrine and ganglion cells in the superfused, isolated retina-eyecup of the rabbit. The putative neurotransmitters aspartate, glutamate, and several of their analogues were added to the superfusate while the membrane potential and light-responsiveness of the retinal neurons were monitored. Both L-aspartate and L-glutamate displayed excitatory actions on the activity of the vast majority of amacrine and ganglion cells studied. However, these agents occasionally appeared to inhibit the responses of the inner retinal neurons by producing hyperpolarization of the membrane potential and blockage of the light-evoked responses. In either case, the effects of aspartate and glutamate were indistinguishable. The glutamate analogues kainate and quisqualate produced strong excitatory effects on the responses of amacrine and ganglion cells at concentrations some 200-fold less than those needed to obtain similar effects with aspartate or glutamate. The aspartate analogue, n-methyl DL-aspartate (NMDLA), also produced strong excitatory effects but was approximately three times less potent than kainate or quisqualate. On one occasion, we encountered a ganglion cell that was depolarized by kainate, but hyperpolarized by NMDLA. The glutamate antagonist alpha-methyl glutamate and the aspartate antagonist alpha-amino adipate effectively blocked the responses of amacrine and ganglion cells. However, on any one cell, one antagonist was always clearly more potent than the other. We examined the actions of the glutamate analogue 2-amino-4-phosphonobutyrate (APB) on the responses of inner retinal neurons and found that it selectively abolished all "on" activity in the inner retina. Together with our finding that APB selectively abolishes on-bipolar cell responses (see Ref. 6), these data support the hypothesis that on-bipolar cells subserve the "on" activity of amacrine and ganglion cells. Our data suggest that aspartate and glutamate are excitatory transmitters in the inner retina, possibly being released from bipolar cell axon terminals in the inner plexiform layer.

Aminobutyrates↗