We examined the effects of temperature on excitatory synaptic transmission and the recurrent inhibitory loop in CA1 neurons in guinea pig hippocampal slices. Increasing the temperature of the perfusing medium from 30 to 49°C resulted in attenuation of both the amplitude of the synaptically evoked CA1 population spikes and the paired-pulse inhibition (PPI) of the spikes. A bath application of 2 μM picrotoxin, a γ-aminobutyric acid receptor antagonist, did not affect the amplitude of the CA1 population spikes, but it significantly reduced PPI during the early heating phase (30-32°C). In contrast, the application of 1 mM theophylline or 50 μM 8-phenyltheophylline, a selective adenosine A1 receptor antagonist, resulted in significant augmentation of the PPI during the early phase of hyperthermia (30-34°C) and a significant increase in the amplitude of the CA1 population spikes at higher temperatures (34-43°C). These results suggest that increased activation of adenosine A1 receptors in response to a temperature increase depresses not only excitatory synaptic responses, but also the strength of the inhibitory circuit in CA1 neurons. Furthermore, hyperexcitability of CA1 pyramidal neurons was seen in the middle of the heating range (34-38°C), excitatory responses still being present, but the strength of the inhibitory circuit significantly reduced.

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The cerebrospinal fluid (CSF) secretion of rat was monitored by longitudinal relaxation time-weighted magnetic resonance imaging (T₁-weighted MRI) in combination with a ventricular injection of a T₁-relaxation reagent: gadolinium-diethylene triamine-N,N,N′,N″,N″-pentaacetic acid (Gd-DTPA). A cannula was inserted in the left lateral ventricle, and 5 &mgr;l of 8.5 mM Gd-DTPA was injected as a CSF marker. Changes in the image intensity of the CSF were measured every 30 s, and the turnover rate of CSF (k) in the left lateral ventricle was obtained from the dilution of Gd-DTPA, based on the assumption of a single compartment model. In the control conditions, k was 0.158 ± 0.009 min⁻¹ at an arterial blood CO₂ tension (pCO₂) of 38.6 ± 2.2 mmHg (n = 10), which corresponds to the CSF secretion rate of 3.6 μl min⁻¹. The k value was decreased (0.078 ± 0.010 min⁻¹, n = 4) by a carbonic-anhydrase inhibitor (acetazolamide). The turnover rate was decreased by hypocapnia (0.094 ± 0.019 min⁻¹, pCO₂ = 24.7 ± 2.9 mmHg, n = 4), and it increased gradually and reached a plateau level as a result of hypercapnia (0.194 ± 0.011 min⁻¹, pCO₂ = 104.5 ± 7.1 mmHg, n = 10). These results suggested that CO₂ upregulates the secretion of CSF in the rat.

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This study focused on the mitochondrial DNA (mtDNA) as the genetic factor most likely to bring about the individual difference in endurance capacity or its trainability. Platelets contain mtDNA but no nuclear DNA, whereas ρ⁰-HeLa cells have nuclear DNA but no mtDNA. The oxidative capacity of mitochondria in the cultured cells, which were fused ρ⁰-HeLa cell with platelets obtained from individual subjects (the so-called "cybrids"), reflects the individual mtDNA polymorphism in the gene-coding region. The purpose of this study was to investigate the relationship between the oxidative capacity of cybrids and the individual difference in endurance capacity, or its trainability. Forty-one sedentary young males took part in an 8-week endurance training program. They were determined by using their VO_{2 max} as an index of endurance capacity on an ergocycle before and after the endurance training program. The relations between VO_{2 max} before endurance training or the change of it by endurance training and the oxidative capacity of cybrids were investigated. There was no relation between them, and two groups were drawn from all subjects, based on one standard division of their initial VO_{2 max}: the higher pre-VO_{2 max} group (n = 6) and the lower pre-VO_{2 max} group (n = 5) (51.8 ± 3.5 ml/min/kg vs. 33.3 ± 3.8 ml/min/kg, p < 0.01). No significant difference was found between the O₂ consumption of the cybrids in the higher initial VO_{2 max} group and that in the lower initial VO_{2 max} group (16.3 ± 4.9 vs. 15.9 ± 2.0 nmol O₂/min/10⁷ cells, NS). Furthermore, neither the cytochrome c oxidase (COX) activity nor the complex I + III activity of cybrids showed a significant difference between the two groups. The oxidative capacity of cybrids between the high trainability group (n = 6) (ΔVO_{2 max} 12.1 ± 1.6 ml/min/kg) and the low trainability group (n = 9) (ΔVO_{2 max} 2.3 ± 0.5 ml/min/kg) was also similar. Thus the mtDNA polymorphism is very unlikely to relate to the individual difference in endurance capacity or its trainability in young sedentary healthy subjects.

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A cation channel from Tetrahymena cilia is permeable to both monovalent and divalent cations. A single-file two-site channel model was introduced for explaining the single channel currents of the channel in mixed solutions of K⁺ and Ca²⁺. In the model it was assumed that two potassium ions or one calcium ion can bind to the binding sites, and that the potassium ions between the binding sites are in a fast equilibrium condition. Single channel currents were calculated from the values of rate constants, ionic concentrations on both sides of the membrane, and the membrane voltages. This model could explain all the observed single channel currents of the channel in K⁺ or Ca²⁺ solution and in mixed solutions of K⁺ and Ca²⁺. The values of the reversal potential in the bi-ionic condition could distinguish this single-file two-site channel model from the single-site channel model or the model in which each ion permeates through the same channel independently (the Goldman-Hodgkin-Katz equation). Experimental data supported this model.

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The present study was carried out to examine the relationship between intracellular free calcium ion concentrations and its regulatory enzymes, sodium potassium adenosine triphosphatase (Na⁺,K⁺-ATPase) and calcium adenosine triphosphatase (Ca²⁺-ATPase), with airway reactivity to inhaled histamine in guinea pigs. Forty-nine guinea pigs were included in this study. Of these, 34 animals responded to histamine bronchoprovocation challenge in vivo with a greater than 35% fall in specific airways conductance and were labeled as "reactive," and the remaining 15 were "nonreactive." The dose of histamine producing a 35% fall in specific airways conductance was labeled as ED₃₅ SGaw. The animals were then sacrificed, and the following biochemical measurements were carried out: intracellular free calcium ion concentrations [Ca²⁺]_i in leukocytes and isolated tracheal smooth muscle cells, activities of Na⁺,K⁺-ATPase and Ca²⁺-ATPase in tracheal homogenate, and plasma levels of lysophosphatidylcholine (LPC). Reactive guinea pigs showed significantly higher [Ca²⁺]_i and Na⁺,K⁺-ATPase and Ca²⁺-ATPase activities. Airway reactivity (ED₃₅ SGaw) had significant negative correlation with [Ca²⁺]_i, with activities of each of the ATPases and with plasma lysophosphatidylcholine. It is concluded that the level of [Ca²⁺]_i is an important determinant of airway reactivity. Intracellular calcium levels modulate airway response to histamine with higher levels being associated with greater reactivity.

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Bile and pancreatic secretions were determined in a CCK-A receptor deficient mouse mutant generated by gene targeting in embryonic stem cells. The targeting vector contained lacZ and neo insertions in exon 2. Under the urethane anesthesia, the common bile duct was cannulated, and the mixture of bile-pancreatic juice was collected every 30 min. After the 1 h basal secretion, CCK-8 (0.5 and 1.0 nmol/kg), acetylcholine (500 nmol/kg), and neuromedin C (1.0 μmol/kg) were injected subcutaneously, and the secretions were collected following 1 h. Amylase and bile acid outputs were determined as parameters of pancreatic secretion and gallbladder contraction, respectively. In some CCK-A receptor (+/−) animals, LacZ staining was performed. CCK-8 significantly increased amylase and bile acid outputs in CCK-A receptor (+/+) and (+/−) mice, whereas no response was observed in (−/−) mice. Neuromedin C and acetylcholine increased amylase secretion in CCK-A receptor (−/−) mice similar to (+/−) and (+/+) mice. The same doses of neuromedin C and acetylcholine could not increase bile acid secretion. The gallbladder smooth muscles, pancreatic acinar cells, duct cells, and islets were stained by LacZ. CCK and CCK-A receptor are important for pancreatic secretion and gallbladder contraction. Neuromedin C and acetylcholine may compensate pancreatic function, but not gallbladder contraction.

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To examine a hypothesis of whether static muscle contraction produces a release of catecholamines from the adrenal medulla via reflex stimulation of preganglionic adrenal sympathetic nerve activity induced by receptors in the contracting muscle, we compared the reflex responses in a concentration of epinephrine (Ep) and norepinephrine (NEp) in arterial plasma during static contraction and during a mechanical stretch of the hindlimb triceps surae muscle in anesthetized cats. Static contraction was evoked by electrically stimulating the peripheral ends of the cut L₇ and S₁ ventral roots at 20 or 40 Hz. Mean arterial pressure (MAP) and heart rate (HR) increased 23 ± 3.1 mmHg and 19 ± 4.3 beats/min during static contraction. Ep in arterial plasma increased 0.18 ± 0.072 ng/ml over the control of 0.14 ± 0.051 ng/ml within 1 min from the onset of static contraction, and NEp increased 0.47 ± 0.087 ng/ml over the control of 0.71 ± 0.108 ng/ml. Following a neuromuscular blockade, although the same ventral root stimulation failed to produce the cardiovascular and plasma catecholamine responses, the mechanical stretch of the muscle increased MAP, HR, and plasma Ep, but not plasma NEp. With bilateral adrenalectomy, the baseline Ep became negligible (0.012 ± 0.001 ng/ml) and the baseline NEp was lowered to 0.52 ± 0.109 ng/ml. Neither static contraction nor mechanical stretch produced significant responses in plasma Ep and NEp following the adrenalectomy. These results suggest that static muscle contraction augments preganglionic adrenal sympathetic nerve activity, which in turn secretes epinephrine from the adrenal medulla into plasma. A muscle mechanoreflex from the contracting muscle may play a role in stimulation of the adrenal sympathetic nerve activity.

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Using a near infrared (NIR) imaging device, we tested the hypothesis that regional differences in oxygen status could be detected in the gastrocnemius muscle during exercise and recovery. Six healthy subjects performed the standing plantar flexion exercises for 2 min; the frequency was one contraction per second. The NIR imaging device was placed over the medial head of the right gastrocnemius muscle and the signals from two optical sensors situated on the middle proximal and middle distal portions were used. The NIR-O₂ saturation (difference between deoxygenated and oxygenated Hb signals) and NIR-blood volume (sum of the oxygenated and deoxygenated Hb signals) were calculated in optical density units. Plantar flexion resulted in more deoxygenation during exercise and more reoxygenation during recovery in the distal portion compared with the proximal portion. The changes in NIR-O₂ between rest and a 2 min exercise, and between a 2 min exercise and a 3 min recovery were 0.11 and −0.23, respectively, in the distal portion, which were significantly larger than proximal values (0.05 and −0.10, p < 0.05). Plantar flexion resulted in lower NIR-blood volumes during exercise and greater recovery of blood after exercise in the distal portion compared with the proximal portion. The changes in NIR blood volume between rest and a 2 min exercise and between a 2 min exercise and a 3 min recovery were −0.19 and 0.31, respectively, in the distal portion, significantly larger than proximal values (−0.07 and 0.12, p < 0.05 for all comparisons). These findings indicate that the distal portion of the medial gastrocnemius had larger changes in NIR-O₂ saturation and NIR-blood volume than the proximal portion had. This is consistent with the distal portion having a greater impairment of blood flow possibly because of the higher intramuscular pressure during exercise. In conclusion: (1) regional differences in oxygen status in the gastrocnemius muscle were detected with exercise, with the distal portion having greater NIR-O₂ saturation and NIR-blood volume changes, and (2) the NIR imaging device might be a useful method to detect the regional differences of oxygen status in the muscle.

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It has been reported that maximal oxygen uptake (VO_{2 max}) is linearly correlated with blood volume (BV) in young people and that there is a reduction in VO_{2 max} with aging. To examine the involvement of BV in the reduction of VO_{2 max}, we used an incremental cycle ergometer protocol in a semirecumbent position to determine the relationship between peak oxygen uptake (VO_{2 peak}) and BV in older subjects (69.1 ± 1.0 years; n = 22), then compared that relationship with that in young subjects (22.3 ± 0.5 years; n = 31). In the present study, VO_{2 peak} and BV were significantly lower in the older subjects, compared with those in the young subjects. A linear correlation was demonstrated between the VO_{2 peak} and BV in both the older (r = 0.705; p < 0.001) and the young (r = 0.681; p < 0.001) subjects within the groups. However, an analysis of covariance with BV as a covariate revealed that VO_{2 peak} at a given BV was smaller in the older subjects than in the young subjects (p < 0.001), i.e., graphically, the regression line determined for the older subjects showed a downward shift. The decreased peak heart rate as a result of aging (153 ± 3 beats/min in the older vs. 189 ± 2 beats/min in the young subjects) contributed partly to this downward shift. These results suggest that the BV is an important determinant factor for VO_{2 peak}, especially within an age group, and that the age-associated decline of VO_{2 peak} is also, to a relatively larger degree, because of factors other than BV and heart rate.

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We report on the optical imaging of spontaneous respiratory neuron bursts in the ventrolateral medulla (VLM) of medullary slices or brain stem-spinal cord preparations. A medullary slice with a thickness of 1.0-1.4 mm or brain stem-spinal cord from 0- to 4-d-old rats was stained with fluorescent voltage-sensitive dye, RH795. Optical signals were recorded as a fluorescence change by using an optical recording apparatus with a 128 × 128 photodiode array and a maximum time resolution of 0.6 ms. Motoneuronal activity was simultaneously recorded at the hypoglossal nerve roots or fourth cervical ventral roots. Fluorescence changes corresponding to the spontaneous inspiratory burst activity were detected in the hypoglossal nucleus and VLM in slice preparations, and in a limited area extending rostrocaudally in the VLM of the brain stem-spinal cord preparation. These measurements did not require signal averaging by multiple trials. Results suggest that inspiratory neurons are localized in more compact form at the level of the nucleus ambiguus than at the more rostral VLM, and that peak activity during the inspiratory phase propagates from the caudal to the rostral VLM. In 60% of brain stem-spinal cord preparations, weak and scattered fluorescence changes preceding the inspiratory burst activity were detected more predominantly in the rostral part of the VLM. The present findings show the feasibility of optical recordings for the in vitro analysis of spontaneous respiratory neuron activity in the medulla.

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Preceding mental sweating response (MSR) during mental stress, small wavelets and large waves are observed on EEG. In the present study, locations of current sources of the large waves were estimated. The results revealed that the current dipole was estimated around the orbits, reflecting activity of the eyelid or eye muscles.

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Although the posterior part of the hypothalamus has long been considered important for thermoregulatory shivering, it is unknown whether the neurons there or the passing fibers are implicated in the response. Exposure of urethane-anesthetized rats to cold (15-21°C) elicits shivering. An injection of muscimol (0.5 mM), a GABA_A receptor agonist, into the medial part of the hypothalamus, including the dorsomedial and posterior nuclei, suppressed the cold-induced shivering. This result suggests that neurons having an excitatory effect on shivering are in this region of the hypothalamus.

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