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T E Dick

Publications and source records attributed to T E Dick.

51 records · Page 3Linked to original sources
PubMed1988

Upper airway pressure receptors alter expiratory muscle EMG and motor unit firing.

To examine the effects of upper airway negative pressure (UAW NP) afferents on respiratory muscle activity during expiration (TE), diaphragm electromyograms (EMG) and triangularis sterni EMG and single motor unit activity were recorded from supine anesthetized tracheotomized cats while they breathed 100% O2. The period of TE during which the diaphragm was electrically active (TE-1) and the period of TE during which the diaphragm was quiescent (TE-2) were both increased with continuous UAW NP (P less than 0.001 and P less than 0.05, respectively), as was TE-1 as a percent of TE (P less than 0.001). Continuous UAW NP reduced peak triangularis sterni EMG (P less than 0.001) and delayed its expiratory onset (P less than 0.005) but did not alter its duration of firing. Changes in triangularis sterni EMG were due to a combination of complete cessation of motor unit activity (2 of 17 motor units), a reduction in mean motor unit firing frequency (P less than 0.02), and a delay in the expiratory onset of motor unit activity (P less than 0.001). Qualitatively similar results were obtained when UAW NP was applied during inspiration only. We conclude that 1) UAW NP has reciprocal stimulatory and inhibitory influences on diaphragm and triangularis sterni muscle electrical activity, respectively, during expiration, and 2) the reductions in triangularis sterni EMG are due to both motor unit derecruitment and a slowing of motor unit firing frequency.

Animals↗
PubMed1988

Repetitive firing properties of phrenic motoneurons in the cat.

1. Using both rectangular- and ramp-shaped intracellularly injected currents, the repetitive firing properties of 23 antidromically identified phrenic motoneurons were determined in anesthetized, paralyzed, and artificially ventilated cats during hypocapnic apnea. In response to rectangular depolarizing current injections, regular repetitive firing was observed in all cells. 2. At the beginning of a rectangular current pulse, the firing pattern was characterized by high frequency of firing that rapidly adapted to a much lower steady-state value. The relationship between the reciprocal of the first interspike interval (F1-2) and injected current was described by an initial linear portion of shallow slope, followed by a much steeper segment that smoothly reached a plateau value. The plateau value of F1-2 did not change with further increase in injected current. 3. The steady-state firing frequency versus injected current relationship was represented by a line of shallow slope over the entire range of injected currents. The slope of this line ranged between 1.1 and 4.5 Hz/nA. 4. A weaker correlation between minimal firing frequency for continuous activity and the reciprocal of the after hyperpolarization duration (1/AHPdur) was found for phrenic motoneurons than exists for lumbosacral motoneurons (26). Comparison of AHP shape at different levels of repetitive firing revealed that the slopes of the ascending portions of the AHP were similar except at the higher injected currents. Further, in the same cells during natural inspiratory activity the ascending part of the AHP was similar to that observed during current injection. 5. Depolarizing current ramps (approximately 1-s duration) were injected into 11 phrenic motoneurons. Instantaneous firing frequency was directly proportional to the intensity of the instantaneous injected current and independent of the rate of change of current for the range of ramp slopes tested (5-80 nA/s). Ramp-and-hold current injections were done in three motoneurons, and the peak instantaneous firing frequency showed little adaptation during the hold maneuver. 6. During hypocapnic apnea, we mimicked the expiratory-phase inhibition and inspiratory-phase excitation of phrenic motoneurons by injecting a 1-s depolarizing current ramp that was immediately preceded by a 1-s hyperpolarizing current ramp of the same absolute peak current intensity. Compared with the effects of positive current ramps alone the spike onsets during the negative-positive current ramp paradigm were either facilitated or retarded. Various ionic mechanisms are suggested for these effects as well as their function in determining the onset of firing during natur

Animals↗
PubMed1987

Serotonin-mediated excitation of recurrent laryngeal and phrenic motoneurons evoked by stimulation of the raphe obscurus.

Short-latency averaged responses in the recurrent laryngeal nerve (RLN) and C5 phrenic nerve to electrical stimulation (2.5-80 microA; 2.5-160 Hz; 150 microseconds pulse duration) of the medullary nucleus raphe obscurus (RO) were investigated in anesthetized, paralyzed and artificially ventilated cats. The response evoked in RLN by stimulation within RO was excitatory and consisted of a single peak. Characteristics of this response in RLN were compared with those of the delayed excitatory response in C5 phrenic nerve, which we previously showed to be elicited by stimulation within RO. Mean latency to onset for the excitatory response in RLN was 5.7 +/- 0.3 ms, while the delayed excitatory response in C5 phrenic nerve occurred at 7.0 +/- 0.3 ms. The excitatory response in both nerves could be evoked when stimulation was applied during inspiration as well as during expiration. The stimulus threshold varied between 2.5 and 5 microA for evoking the inspiratory-phase response in each nerve. The magnitude of this response in RLN and in C5 phrenic nerve was directly related to current intensity and was dependent upon stimulus frequency. Intravenous administration of the serotonin receptor antagonist, methysergide (0.1-2.4 mg/kg) caused significant dose-related reductions in the response in each nerve. In summary, characteristics of the evoked response in RLN and phrenic nerve are similar in several ways. Both responses are: (1) excitatory in nature, (2) elicited at small stimulus currents, (3) affected similarly by increasing stimulus current and frequency, (4) elicited by stimulation during inspiration and expiration, and (5) mediated at least in part by activation of pathways using serotonin as a neurotransmitter.

Animals↗
PubMed1987

Correlation of recruitment order with axonal conduction velocity for supraspinally driven diaphragmatic motor units.

Spontaneous activities of pairs of single diaphragmatic motor units (MUs) were recorded via two electrodes in anesthetized cats, ventilated with CO2 added to the inspired gas, which slightly enhanced respiratory drive (endtidal CO2 less than 6%). These MUs were characterized by their axonal conduction velocities (CVs) and relative onset times (defined as the time after onset of phrenic nerve activity until the MU began discharging divided by the duration of inspiration). Motor unit axonal CV was estimated by the conduction time and the distance between two points on the phrenic nerve. Results were compared from two experimental preparations: one with dorsal roots intact and the other with dorsal roots transected bilaterally between fourth (C4) and seventh (C7) cervical segments. Estimated mean CV for phrenic MUs was 46.2 m/s(n = 180 MU). Motor units were classified as early and late recruited MUs depending on their relative onset times. We correlated MU axonal CV with its relative recruitment time. A highly significant (P less than 0.0001), positive correlation between axonal CV and relative recruitment time was established for those diaphragmatic MUs recruited with this respiratory drive. Correlation coefficients were r = 0.70 for intact animals, r = 0.72 for dorsal rhizotomized animals, and r = 0.72 overall population. For pairs of MUs, the CV of the earlier recruited unit was compared with the CV of the later recruited unit. In 96% of pairs from intact animals and 92% of pairs from dorsal rhizotomized animals, the first MU had a lower CV than the MU recruited later. Difference in relative times of recruitment was directly related to difference in axonal CVs. However, a portion of the motor pool with high-axonal CVs was not sampled. Under conditions of these experiments, afferent input in cervical dorsal roots, including that from diaphragmatic receptors, did not influence the distribution of MU relative onset times. Further, a similar proportion of MU pairs wherein the earlier recruited MU had a CV lower than the later recruited unit was observed in intact and dorsal rhizotomized animals. We also cross-correlated 31 pairs of simultaneously recorded MUs to assess common input onto phrenic motoneurons. Common input was characterized by the presence of peaks having widths of greater than or equal to 3 ms in the cross-correlation histograms (CCHs) and occurring within 20 ms of the trigger event. Peaks were judged significant if the bin with the largest number of occurrences was significantly greater than base line and if neighboring bins were above base line.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1987

Electrical properties of phrenic motoneurons in the cat: correlation with inspiratory drive.

1. Resting membrane potential (Vmp), input resistance (Rn), rheobase (Irh), and after hyperpolarization duration (AHPdur) and amplitude (AHPamp) were measured in 38 phrenic motoneurons of anesthetized, paralyzed, and artificially ventilated cats during hypocapnic apnea. The mean +/- SD and range of values for these variables were as follows: Vmp, -68 +/- 5mV (range: -60 to -82); Rn, 1.3 +/- 0.6 M omega (0.6-2.4); Irh, 9.7 +/- 5 nA (2-20); AHPdur, 68 +/- 19 ms (37-134); AHPamp, 3.3 +/- 1.8 mV (1.0-8.5). In 31 motoneurons, the membrane potential level at which firing occurred (Vthr) during intracellular current injection was measured. The mean value of Vthr was -58 +/- 3 mV (range: -52 to -64). 2. A histogram of Rn revealed a bimodal distribution. Also a plot of Irh against Rn showed a grouping of the motoneurons into two subpopulations: 1) low-Rn and high-Irh cells, called type L neurons, and 2) high-Rn, low-Irh cells, called type H neurons. The overall negative linear correlation between Irh and Rn (r = -0.85; P less than 0.0001) resulted from this grouping rather than from a strictly linear relation between these two variables. 3. Electrical properties were compared for type L (n = 20) and type H (n = 18) phrenic motoneurons. The following mean values were found for each group, respectively: Rn, 0.8 and 1.8 M omega; Irh, 13.7 and 5.3 nA; AHPdur, 58 and 79 ms; AHPamp, 2.4 and 4.4 mV. All differences were significant (t test, P less than 0.001). Mean Vthr was the same for the two groups. 4. Comparison of these data with those available for lumbosacral motoneurons revealed that almost all investigated electrical properties of type L and type H phrenic motoneurons are similar to the analogous properties of type F (fast twitch) and type S (slow twitch) lumbosacral motoneurons, respectively. The apparent exception is the lower mean value of Irh for type L phrenic motoneurons compared with type F lumbosacral motoneurons. 5. For 13 cells, membrane potential was continuously monitored while spontaneous respiratory activity was restored by increasing CO2. It was found that at approximately the same end-tidal CO2 (about 7%) and a similar end-expiratory mean membrane potential level (approximately -70 mV), mean amplitude of peak inspiratory synaptic depolarization was higher in type H motoneurons (8.8 mV, n = 5) than in type L (2.9 mV, n = 8; P less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Connectivity of slowly adapting pulmonary stretch receptors with dorsal medullary respiratory neurons.

1. Intracellular recordings were made from 50 dorsal respiratory group (DRG) neurons in the region of the ventrolateral nucleus of the solitary tract in anesthetized, paralyzed cats ventilated with a cycle-triggered pump whose inflation stroke was triggered by the onset of phrenic nerve inspiratory (I) discharge. Activity was recorded simultaneously in the ipsilateral nodose ganglion from sensory cell bodies of slowly adapting pulmonary stretch receptors (PSRs). 2. Respiratory cycle-related membrane potential changes of DRG neurons were recorded. Twenty-six neurons that did not exhibit spikes were classified as I alpha, I beta or pump (P)-cells by comparing their membrane potential trajectories during I in the presence of lung inflation with that observed during I, but with lung inflation withheld. The remaining 24 neurons were classified similarly, but the classification was based upon a comparison of their I-phase spike activity responses with and without lung inflation. I phase-related histograms of either membrane potential or spike activity were constructed to facilitate DRG neuronal classification. Additionally, steady lung inflation of varying magnitudes was applied during the expiratory phase. This prolonged expiration and produced different responses in the neurons. Generally, I beta and P-cells were depolarized, whereas I alpha cells were hyperpolarized. 3. Low-intensity electrical stimulation of the ipsilateral vagus nerve evoked excitatory postsynaptic potentials (EPSPs) in all three DRG neuronal types. P-cells and I beta cells exhibited EPSPs in response to the lowest intensity; generally this intensity was below threshold for the simultaneously recorded PSR. Overall, EPSPs in I alpha cells had the highest thresholds, but some EPSPs could be evoked at thresholds similar to those of the I beta cells. The distributions of the average onset latency of the evoked EPSP overlapped considerably. Thus vagal electrical stimulation cannot be used for unequivocal classification of DRG neurons into I alpha, I beta, and P-cell subpopulations. 4. Using intracellular spike-triggered averaging, single PSRs were shown to generate monosynaptic EPSPs in I beta neurons and P-cells but not I alpha cells. Divergence of single PSR afferents also was observed. Relationships between EPSP shape factors, amplitudes, and PSR afferent conduction velocity are similar to those previously observed for monosynaptic EPSPs in hindlimb motoneurons generated by spinal afferents.

Animals↗
PubMed1986

Involvement of serotonin in the excitation of phrenic motoneurons evoked by stimulation of the raphe obscurus.

Short-latency averaged responses in the C5 phrenic nerves to electrical stimulation (2.5-80 microA; 5-80 Hz; 150 microseconds pulse duration) of raphe pallidus (RP) and raphe obscurus (RO) were investigated in anesthetized, paralyzed, and artificially ventilated cats. The responses to stimulation of RO were excitatory, whereas a mixture of inhibitory and excitatory responses of lesser magnitude were observed after stimulating in RP. The maximal response was obtained from the ventral part of RO and consisted of early and delayed excitatory responses that were of equal magnitude in both left and right C5 phrenic nerve roots. The mean latency for the early response was 2.5 +/- 0.1 msec and for the delayed response was 7.0 +/- 0.2 msec. Both responses were elicited during inspiratory phase stimulation, but only the delayed response was present during expiratory phase stimulation. The stimulus threshold of the early response was 5 microA; the delayed response was elicited at currents as small as 2.5 microA. Early and delayed responses were affected in different ways by increasing stimulus current and by increasing stimulus frequency. Intravenous administration of serotonin receptor antagonists methysergide (0.1-0.7 mg/kg), metergoline (33-244 micrograms/kg), and cinanserin (1.5-9.0 micrograms/kg) caused significant dose-related reductions in the magnitude of the delayed response, but did not significantly affect the early response. These data suggest that the early and delayed excitatory responses are mediated by different neuronal pathways. The early response does not involve serotonin release, while the later response is mediated at least in part by activation of a serotonergic pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Axonal projections of single bulbospinal inspiratory neurons revealed by spike-triggered averaging and antidromic activation.

Activity was recorded extracellularly from 26 inspiratory bulbospinal neurons in anesthetized, paralyzed, artificially ventilated cats. All but one were located in the ventral respiratory group. A neuron was classified as either I alpha or I beta by comparing its firing pattern during inspiratory cycles with lung inflation to its pattern when lung inflation was withheld during the central inspiratory phase (2, 14, 15). In this study, the projection and conduction velocity of these axons were determined using two methods: antidromic activation (AA) of the bulbospinal neurons and spike-triggered averaging (STA) of the extracellular field potentials. These methods have been compared directly because the same electrode was used both for stimulating the axon of the bulbospinal neuron and recording its axonal potential in the same location. Axonal projections from these neurons were mapped in the contralateral spinal cord with a mobile electrode by determining where the lowest stimulus threshold occurs for AA and greatest axonal potential can be recorded with STA. The locations of these axons were in the ventral and lateral funiculi. Each method determined a similar location for an axon. Positions of 10 axons were determined at both the third (C3) and fourth (C4) cervical segments. Single axons maintained their positions in either descending tract from rostral C3 to mid-C4. In five of six cases where two "neighboring" medullary units were characterized, the axons of each pair projected together within 350 micron of each other in the cervical spinal cord. Estimates of mean axonal conduction velocity (CV) from antidromic activation from a single stimulus site, "single-point AA," were as much as 42% less than corresponding estimates from STA extracellular field potentials at that point (P less than 0.001). Such single-point estimates were less than determinations that were calculated from the difference in conduction time and the difference in conduction distance from two points in the spinal cord. These two-point determinations averaged 55.4 +/- 13.1 m/s (using AA) and 53.3 +/- 13.1 (using STA) for 10 neurons. These values were not significantly (P greater than 0.2) different from each other and are greater than most earlier reports, which used the single-point AA method. Either method, AA or STA, can be used to determine axonal position and CV. The advantages and disadvantages of each method are discussed.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Intercostal muscle activity of the cat in the curled, semiprone sleeping posture.

We examined the effect of different sleeping postures on intercostal muscle activity in the cat. Cats assume a variety of sleeping positions, but the semiprone, curled position with one side bearing most of the weight was the posture studied in these experiments. In this posture the cat's head rests upon the forepaws and may be slightly tilted. A lateral and ventral curvature of the spine and a lateral flexion of the neck form a curl with an upward-concave side and a downward-convex side. We examined the differences in intercostal activity on the concave and convex sides in this semiprone curled position in seven adult cats. Activity was studied at 14 sites (7 showing inspiratory and 7 showing expiratory activity). Inspiratory intercostal muscle activity was in all cases greater on the concave-upward side; similarly, expiratory intercostal muscle activity was, with the exception of activity at one site, greater on the concave-upward side than on the convex downward side. This effect was evident in rapid eye-movement (REM) as well as nonrapid-eye-movement (NREM) sleep.

Animals↗
PubMed1984

Central and peripheral receptors in guinea-pigs exposed to simulated high altitude.

Guinea-pigs, chronically exposed to simulated high altitude of 6000 m, showed alterations in some, but not all, neurotransmitter-receptor systems. Thus, peripheral (cardiac) beta-adrenergic receptors were decreased in numbers (Bmax) with an increased affinity although no alterations in endogenous cardiac norepinephrine content were found. In contrast, H1-histamine receptors in the guinea-pig ventricle and brain showed no changes in Bmax or affinity. Dopamine receptors of the caudate nucleus showed no differences between control and altitude-exposed guinea-pigs, although previous reports demonstrated a significant increase (19%) in the content of endogenous dopamine of the caudate. Thus, chronic exposure to simulated high altitude altered beta-adrenergic receptors so that they were more sensitive to small ligand concentrations and less sensitive to large ligand concentrations.

Altitude↗
PubMed1982

Intercostal muscle activity during sleep in the cat: an augmentation of expiratory activity.

Intercostal-muscle activity (I-EMG) was studied in sleep and wakefulness in ten adult cats. The animals were implanted with electrodes for recording the electroencephalogram (EEG), electrooculogram (EOG), and pontogeniculooccipital (PGO) waves as well as intercostal- and neck-muscle activity. A small-animal pneumotachograph connected to a tracheal cannula was used to monitor respiration. The data were obtained in 87 recording sessions, each lasting 5-6 h. Total EEG power (fast Fourier analysis) and integrated I-EMG activity were computed over consecutive 5.12-sec periods of wakefulness and nonrapid eye movement (NREM) sleep. Cycle-triggered histograms based on 50 breaths were computed also in wakefulness and NREM sleep. I-EMG was classified as expiratory or inspiratory according to when the activity was maximal during the respiratory cycle. Expiratory I-EMG augmented progressively during NREM sleep with the maximal activity occurring just before rapid eye movement (REM) sleep. The mean correlation between total EEG power and expiratory I-EMG for all expiratory muscles was 0.441 (+/- 0.16 SD; n=24). In contrast to the consistent augmentation of expiratory I-EMG, inspiratory I-EMG changes from wakefulness to deep NREM sleep varied within and between muscle groups: in 21% of the cases, activity decreased from wakefulness to NREM sleep; in 16% of the cases, activity increased; in 56% of the cases, activity did not change; and in 7% of the cases, activity increased in only the expiratory phase. We conclude the consistent augmentation of expiratory intercostal muscle indicates an active, NREM sleep-specific respiratory process that may have important implications for lung mechanics in that state.

Animals↗
PubMed1979

Inhibition of intrapituitary thyroxine to 3.5.3'-triiodothyronine conversion prevents the acute suppression of thyrotropin release by thyroxine in hypothyroid rats.

Iopanoic acid has been shown to block thyroxine (T4)-5'-monodeiodination in rat anterior pituitary in vitro. To test the hypothesis that the acute decrease in thyrotropin (TSH) after infusion of T4 into hypothyroid rats requires intrapituitary T4 to 3,5,3'-triiodothyroxine (T3) conversion, the effect of iopanoic acid treatment on the generation of nuclear T3 from intrapituitary conversion and the response to TSH were compared in control and iopanoic acid-treated animals. 5 mg/100 g body weight iopanoic acid given 24, 16, and 1.5 h before administration of 125I-T4 reduced the quantity of pituitary nuclear 125I-T3 from local (intrapituitary) T4 to T3 conversion by 60-100%. In association with inhibition of intrapituitary T4 to T3 conversion, there was an increase in the binding of 125I-T4 to the nuclear receptor of the pituitary but the total iodothyronine content of the nuclei was still less than half of the nuclear iodothyronine in control animals. Iopanoic acid did not affect the nuclear/plasma ratio of injected 131I-T3 in the same animals, but did appear to impair 131I-T3 clearance or reduce its distribution volume. Treatment with iopanoic acid did not reduce the quantity of nuclear 125I-T3 in the liver, kidney, or heart of the same animals more than expected from the changes in serum 125I-T3. In control hypo-thyroid animals pretreated with iopanoic acid, the mean TSH was not significantly decreased from the initial value by T4 injection. Iopanoic acid pretreatment did not interfere with the acute TSH response of chronically hypothyroid rats to 70 ng of T3/100 g body weight. These results establish that intrapituitary generations of T3 from T4 is required for the acute decrease in TSH which occurs after T4 infusion. The data also are consistent with the content that it is nuclear binding of the T3 generated from T4 which initiates the inhibition of TSH release.

Animals↗
PubMed1978

The contribution of local tissue thyroxine monodeiodination to the nuclear 3,5,3'-triiodothyronine in pituitary, liver, and kidney of euthyroid rats.

The contributions of local T4 monodeiodination and plasma T3 to the nuclear T3 of anterior pituitary, liver, and kidney were measured in euthyroid rats. After injection of [125I]T4, there was a gradual increase in the quantity of plasma [125I]T3 in excess of injected contaminant, which peaked at approximately 12 h after injection and remained a constant fraction of plasma [125I]T4 (2.8 X 10(-3) after that time. In the nuclei of anterior pituitary tissue, there was also a slow increase in locally produced [125I]T3 (in excess of that which could be accounted for by plasma [125I]T3) which appeared to peak at about 16 h after [125I]T4 administration. The ratio of nuclear [125I]T3 generated intracellularly to plasma [125I]T4 was constant at 18 and 24 h after T4 injection and was 13 +/- 2 X 10(-3) in nuclei of pituitary, 2.0 +/- 0.4 x 10(-3) in liver, and 0.47 +/- 0.1 x 10(-3) in kidney (all values are mean +/- SD). This locally generated T3 resulted in a markedly higher nuclear to plasma (N:P) ratio for [125I]T3 than for injected [131I]T3 in the same animals. The N:P ratio for [125I]T3 at equilibrium after injected T4 was 2.4 +/- 0.6, 0.47 +/- 0.09, and 0.10 +/- 0.03 (nanograms of T3 (mg DNA)-1/ng T3 ml-1) in pituitary, liver, and kidney. Comparable values for [131I]T3 N:P ratios were 0.47 +/- 0.14 (pituitary), 0.18 +/- 0.01 (liver), and 0.036 +/- 0.008 (kidney). Using RIA values for plasma T4 and T3 concentrations in these rats and maximal nuclear T3-binding capacities estimated in parallel experiments, the gravimetric quantities of nuclear T3 derived from plasma T3 and from local T4 to T3 monodeiodination were estimated and expressed as the percentage of saturation of T3 receptors. Seventy-eight percent of nuclear T3 receptor sites in anterior pituitary were occupied with one-half of the nuclear T3 derived directly from plasma T3 and the other half from intrapituitary T4 monodeiodination. Local T4 monodeiodination provided only 28% and 14%, respectively, of the nuclear T3 in liver and kidney, and the nuclear receptors of these tissues were about 50% saturated. Since our previous studies have shown that the occupancy of the pituitary nuclear T3 receptors may regulate TSH release, these data provide a mechanism by which TSH secretion could be altered by changes in either plasma T3 or T4, whereas nuclear T3 in liver and kidney is predominantly a function of the plasma T3 concentration.

Animals↗
PubMed1977

Role of transport systems in amino acid metabolism: leucine toxicity and the branched-chain amino acid transport systems.

The livR locus, which leads to a trans-recessive derepression of branched-chain amino acid transport and periplasmic branched-chain amino acid-binding proteins, is responsible for greatly increased sensitivity toward growth inhibition by leucine, valine, and serine and, as shown previously, for increased sensitivity toward toxicity by branched-chain amino acid analogues, such as 4-azaleucine or 5',5',5'-trifluoroleucine. These phenotypes are similar to those of relA mutants; however, the livR mutants retain the stringent response of ribonucleic acid synthesis. However, an increase in the rate of transport or in the steady-state intracellular level of amino acids in the livR strain cannot completely account for this sensitivity. The ability of the LIV-I transport system to carry out exchange of pool amino acids for extracellular leucine is a major factor in leucine sensitivity. The previous finding that inhibition of threonine deaminase by leucine contributes to growth inhibition is confirmed by simulating the in vivo conditions using a toluene-treated cell preparation with added amino acids at levels corresponding to the internal pool. The relationship between transport systems and corresponding biosynthetic pathways is discussed and the general principle of a coordination in the regulation of transport and biosynthetic pathways is forwarded. The finding that the LIV-I transport system functions well for amino acid exchange in contrast to the LIV-II system provides another feature that distinguishes these systems in addition to previously described differences in regulation and energetics.

Biological Transport, Active↗