Great advances in studies on the mechanisms of stimulus reception and transmission in hair cell organs have been made. With the use of intracellular recording, mechanisms related to transduction have been elucidated. The cochlea possesses mechanisms much more sophisticated than in other hair cell organs. In this review, the author attempted to explain these points, in relation to investigation on the goldfish sacculus (i.e. its inner ear).

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The role of Ca²⁺ and calmodulin in stimulation of the rat pancreatic acini induced by secretin, forskolin, and dibutyryl cyclic AMP (dbcAMP) was studied using W-7, a calmodulin antagonist, and a low Ca²⁺ medium. The time course of amylase secretion was studied in a perifusion system using dispersed rat pancreatic acini. The amylase release patterns of each secretagogue were as follows: a biphasic amylase release pattern under the stimulation of secretin, a one peak pattern during the stimulation of forskolin and a rapid response after cessation of the stimulation, and a gradual increased pattern during the stimulation of dbcAMP followed by a rapid response. The amylase release under the stimulation by forskolin and dbcAMP was slightly weaker as compared with that of secretin stimulation. The amylase secretion stimulated by secretin (5×10^-7M), forskolin (50μM), and dbcAMP (2mM) was inhibited by W-7 (50μM). In a low Ca²⁺ medium (4.7-5.1×10^-6M), the secretory rate did not increase during the stimulation by secretin, forskolin, and dbcAMP, and a rapid amylase response remained after cessation of the stimulation of forskolin and dbcAMP. The pretreatment with EDTA (1mM) suppressed both the gradual amylase release and the rapid response induced by dbcAMP in a low Ca²⁺ medium. These results suggested that each secretagogue, via cyclic AMP (cAMP), induced a different amylase secretory pattern dependent on an intracellular Ca²⁺ content, and was mediated by the Ca²⁺-calmodulin complex.

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A comparison is made of the elastic response of fresh pericardial tissues at 25, 37, and 42°C, and also of fresh and glutaraldehyde-fixed tissues. Strips of bovine pericardial tissues cut perpendicular to the base-apex axis of the heart were used. An Instron machine was used for uniaxial tensile tests, and the strain-rate used was 666.7%•min^-1. No significant differences in tissue mechanical properties were observed for temperature values of 25, 37, and 42°C. However tissues fixed in a glutaraldehyde solution were more extensible than fresh tissues. The elastic responses of tissues preserved for 1 day in glutaraldehyde are not very different from those preserved for up to 10 days.

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An electromagnetic flow probe was chronically implanted around the common carotid, superior mesenteric, or renal artery in spontaneously hypertensive rats (SHR). An indwelling catheter was inserted into the terminal aorta for measurement of arterial pressure. Peripheral resistance was calculated by dividing arterial pressure by flow. Decrease in peripheral resistance on ganglion blockade with hexamethonium bromide was assumed to indicate the presence of vasoconstrictor tone to regional resistance vessels. In the conscious, resting state, peripheral resistance decreased significantly on ganglion blockade in the carotid and renal areas but not in the superior mesenteric area. The magnitudes of the decrease in peripheral resistance in the carotid and renal areas were not greater than the respective, corresponding values in normal rats. Presumably, vasoconstrictor tone in these three vascular regions, being quite different from that in the hindquarters, is not higher in SHR than in normal rats. Venomotor tone does not seem to be elevated in conscious SHR either, because the decrease in the sum of the mean peripheral flows on ganglion blockade, which was assumed to reflect the decrease in cardiac output, was not larger in SHR than in normal rats. Pentobarbital anesthesia did not abolish renal vasoconstrictor tone in SHR as it does in normal rats.

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High K⁺-induced hyperpolarization was recorded intracellularly from the snail neurons, Euhadra subnimbosa, and the ionic mechanism underlying this hyperpolarization was analyzed in comparison with the ACh-induced hyperpolarization of the same cell, the latter known to be Cl^--dependent. 1) The membrane resistance always decreased during both hyperpolarizing responses to high K⁺ (24mM) and ACh (0.1mM). 2) Both hyperpolarizing responses to high K⁺ and ACh were reversed in Cl^--free Ringer to the depolarizing responses. 3) Both hyperpolarizing responses to high K⁺ and ACh were markedly augmented immediately after returning to normal Cl^- from Cl^--free Ringer perfusion. 4) Increase in intracellular Cl^--concentration by a leak from KCl-electrode reversed both hyperpolarizing responses to high K⁺ and ACh. 5) Reversal potential of high K⁺-response was always 10-20mV more positive than that of ACh-response, when measured in normal Ringer perfusion. 6) Intracellular Cl^--concentration of the cells which were hyperpolarized by high K⁺ was estimated to be one half of that of the cells which were depolarized by high K⁺ . Above results indicated that the high K⁺-induced hyperpolarization is due to the permeability increase of the postsynaptic membrane toward Cl^-, masking the depolarizing effect of high K⁺ on the same membrane.

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Changes in the oxygenation properties and the relevant biochemical parameters of canine blood were followed during its storage in acid-citrate-dextrose (ACD) medium (4°C) and after transfusion of the stored blood. Reductions of the blood P₅₀ (pH 7.40, P_CO2 40Torr, 37°C) and 2, 3-diphosphoglycerate (DPG) during storage was much slower than in human blood. Half-decay time for DPG was 21 and 5 days for canine and human blood, respectively. The DPG decay could be extensively accelerated in the presence of bisulfite in ACD. The stored and DPG- depleted red cells required a considerably long period of time for the complete posttransfusional restoration of the DPG and P₅₀. In five dogs whose blood were exchanged by 84% in average with the stored blood of mean DPG depletion of 88%, mean extents of the DPG and P₅₀ restoration were 74 and 89% of the normal values after 24h. After 5 days both the parameters were within the normal ranges. The red cell extra- along with intra-cellular pH fell immediately after the transfusion, and restored to the normal level after 24h. From these results, correlations between P₅₀ or red cell transmembrane pH gradient at the extracellular pH of 7.40 (ΔpH) and red cell DPG/hemoglobin molar ratio (x) were derived as P₅₀=10.92x+14.2 (r=0.91) or ΔpH=0.60x+0.135 (r=0.70).

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In 55 anesthetized and paralyzed adult rabbits, 161 spontaneously active neurons which responded to electrical stimulation of A-fibers of the aortic nerve were found within the ventrolateral medulla (VLM). They were termed barosensory VLM neurons, since the aortic nerve A-fibers were considered to consist exclusively of afferents from arterial baroreceptors. Forty percent of barosensory VLM neurons tested (49/123) were activated antidromically by stimulation of the dorsolateral funiculus indicating that they send descending bulbospinal projections. Spontaneous discharges of barosensory VLM neurons were invariably inhibited by stimulation of aortic nerve A-fibers. Ninety-three percent of 80 neurons tested also responded to stimulation of aortic nerve C-fibers, a mixture of barosensory and nonbarosensory afferents. Natural stimulation of carotid sinus baroreceptors by an intravenous injection of phenylephrine in 19 vagotomized rabbits with aortic nerves disrupted inhibited spontaneous activity of all the 50 barosensory VLM neurons tested. By contrast, pharmacological stimulation of right or left carotid body chemoreceptors by close arterial injection of NaCN into the carotid sinus augmented activity of 93% of barosensory VLM neurons tested (41/44). The neuronal response was always greater to stimulation of chemoreceptors in the contralateral carotid sinus. Seven out of 8 barosensory VLM neurons tested (88%) were orthodromically excited by stimulation of the posterior hypothalamic area. In 74% of the 97 neurons examined in 29 vagotomized animals, a distinct respiratory-related rhythm, locked to that of phrenic nerve activity, was discerned. Thus, spontaneous activity of barosensory VLM neurons is inhibited by afferent inputs from aortic and carotid sinus baroreceptors, but is excited by incoming signals from carotid body chemoreceptors and the posterior hypothalamic area. It is also subject to the influence of the central mechanism generating the respiratory rhythm.

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We investigated the temporal and spatial interactions between the carotid sinus and aortic arch baroreflex control of arterial pressure in 25 dogs anesthetized with pentobarbital sodium. The carotid sinus baroreceptor region was vascularly isolated to control the intracarotid sinus pressure. A hemorrhage catheter was inserted into the aortic arch. The systemic arterial pressure change after quick mild hemorrhage (2ml/kg body weight within 1-2s) was monitored. The open-loop gain of the vagally mediated baroreflex system was estimated from the mean arterial pressure response to the hemorrhage. Three protocols were employed to analyze the interactions. In the first protocol, we determined the effect of different levels of intracarotid sinus pressure on the open-loop gain of the vagally mediated baroreflex system. There was no significant effect. In the second protocol, the open-loop gain of the carotid sinus baroreflex system was determined after vagotomy. In the third protocol, the vagally mediated baroreflex system was activated by the hemorrhage without (spatial interaction) or with (temporal interaction) a delay after changing the intracarotid sinus pressure. The spatial interaction was facilitatory. A temporal interaction was found between the carotid sinus and vagally mediated baroreflex systems, when the delay was less than 30s.

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The effects of Ca²⁺ and calmodulin on contraction of saponin-treated (chemically skinned) uterine smooth muscle fibers of pregnant rats were examined. Ca²⁺ sensitivity, defined as the pCa required for half maximum activation of force production, was found to change with the progress of pregnancy; low in the early and middle stages and high in the later stages of pregnancy. The overall change of Ca²⁺ sensitivity was about pCa 1.5 during the period of pregnancy. The effect of calmodulin on contraction was also found to be dependent on the stages of pregnancy. Calmodulin was effective on the augmentation of the tension rather than the change in Ca²⁺ sensitivity, and this augmentation was large in the early and middle stages of pregnancy. The amount of calmodulin, which eluted out of uterine muscle cells during saponin treatment, was large in the early and middle stages of pregnancy. The results indicate that the contractile response of the uterine muscle cells during the period of pregnancy seems to be controlled by both the changes in Ca²⁺ sensitivity and in the amount of free calmodulin in uterine muscle cells.

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The effect of airway anaesthesia by lidocaine inhalation on the hypoxic ventilatory response was examined together with the heart rate response by the isocapnic progressive hypoxia test in human subjects. During the test, end-tidal P_CO2 (PET_CO2) was maintained at the resting level. However, because resting PET_CO2 tends to decrease by airway anaesthesia, we conducted the test at the resting PET_CO2 determined both before (normocapnic) and after lidocaine (hypocapnic). Ventilatory and heart rate response were evaluated as a linear function of oxygen saturation of the arterial blood (Sa_O2). In the "hypocapnic" runs, ventilatory responses tended to be depressed, while the slope of heart rate response-PET_CO2 relationship increased after lidocaine. However, when PET_CO2 was restored to the normocapnic level, ventilation apparently increased from the control, and the augmented slope in the heart rate response disappeared. Although the elevated ventilation in normocapnic hypoxia might be due simply to the increased ventilatory response to CO₂, we suggested that the augmented slope in the heart rate response in hypocapnic hypoxia might be related not only to PET_CO2 level itself but also to the direct effect of airway anaesthesia.

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Absorbance responses posterior to action potentials were recorded from frog twitch fibers loaded by an impermeant potential probe dye NK2935 that was chemically identical with WW781. Extracellularly loaded NK2935-related responses (EOS) increased in absorbance around 640nm wavelengths and were like action potential in waveform but were slightly preceded by action potential. Model analysis showed that EOS consisted of two components, namely 39% non-delay component reflected with sarcolemma action potential and 61% first-order delay component reflected with transverse tubule (T) action potential (delay-constant τ1= 0.48ms). The T-disrupted fibers showed only the non-delayed response. Intracellularly injected NK2935-related responses (IOS) were also composed of a single spike of the same direction swing as in the EOS case described by the term "ipsidirection, " but were clearly preceded by EOS and followed by Ca transient, birefringence, transparency and latency relaxation responses. The T-disrupted fibers showed a small "sidedness" response characterized by both opposite direction swing, namely "contradirection" and non-delay against EOS. Model analysis showed that IOS consisted of two main components, namely second-order delay component with ipsidirection (τ₂=0.8ms) and the further high-order delay component with contradirection. Based on spatio-temporal heterogeneity of NK2935 binding inside fibers and potential-absorbance relation in sarcolemma, the former origin was thought to be in junctional sarcoplasmic reticulum (jSR) responding to T excitation with a transient "positive polarization" estimated roughly 20mV. Similarly, the latter was possibly in free SR where a slow "negative polarization" estimated -0.9mV might appear associated with Ca release.

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The time course of GH secretion in response to hpGRF and its dependency on the extracellular Ca²⁺ concentration were studied in perifused dispersed anterior pituitary cells. The onset of GH secretion in response to 1nM hpGRF was relatively rapid (within 5s) but removal of hpGRF after 10-min application further increased the rate of secretion (off-response). The threshold and maximum concentrations of hpGRF in stimulatory secretion were 10^-12 and 10^-8M respectively. Between these two concentrations, the responses showed dose dependency. A reduction in the extracellular Ca²⁺ concentration to 0.25mM or to nominally zero reduced hpGRF-induced GH secretion to 64.4% or to 1.9%, respectively, of the control response in the presence of 2.5mM Ca²⁺. Two mM Co²⁺, known as a strong calcium channel blocker, completely suppressed hpGRF-induced GH secretion. The removal of Ca²⁺ from the perifusion buffer immediately after the offset of 1min-applied 1nm hpGRF accelerated the falling phase of GH secretion, which is parallel to the decline in [Ca²⁺]_o in the perifusion chamber. Under nominal Ca²⁺-free conditions, hpGRF produced no increase in GH secretion. However, 10min after the offset of 1min-applied hpGRF under Ca²⁺-free conditions, the introduction of normal buffer containing 2.5mM Ca²⁺ substantially restored GH secretion, although after 20min the introduction of normal buffer produced only a slight increase in GH secretion. In perifusion experiment of 10⁶ cells, intracellular cyclic AMP (cAMP) content was raised from the basal value of 4 to 26pmol by 2-min application of 1nM hpGRF. After cessation of hpGRF application, cAMP content decreased to 8.7pmol at 11min and returned to the basal value by 20min. The same tendency was observed in Ca²⁺-free buffer. In conclusion, the extracellular Ca²⁺ was essential for hpGRF-induced GH secretion. This indicates the importance of the influx of Ca²⁺ in response to hpGRF. The time course of hpGRF-induced rise and fall in cAMP content was roughly parallel to the GH secretion. The possible explanations of the off-response and the restoration of GH secretion by reintroducing normal buffer were discussed.

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The purpose of the present study was to obtain the immediate CO₂ storage capacity at the onset of exercise. The CO₂ stores at the onset of the exercise were calculated from the difference between the respiratory gas exchange ratio (R) and the metabolic gas exchange ratio (RQ; R obtained at 5.5min of exercise). The CO₂ stores per body weight (CO₂ stores/w) were linearly related to the CO₂ pressure (P′^V_CO2) determined by the CO₂ rebreathing method (r=0.713, p<0.001), the slope being 0.330ml/(mmHg•kg). The CO₂ stores were then corrected for change in O2 stores with exercise, that defined as total CO₂ stores. P′VCO₂ was also corrected for the effect of lung-bag volume shrinkage and Haldane effect during CO₂ rebreathing, that defined as true PVCO₂. The total CO₂ stores/w were also related linearly to the true P′^V_CO2 (r=0.725, p<0.001), the slope of the regression line defined as the immediate CO₂ storage capacity being 0.650ml/(mmHg•kg).

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Effects of footshocks (FS) on antidiuretic hormone (vasopressin, VP) in the plasma were studied in rats. Continuously applied FS of 60s period with 5ms pulses at 50Hz frequency significantly increased VP as well as adrenocorticotrophic hormone (ACTH) in the plasma in a time- and shock intensity-dependent manner. Contrarily, the 50Hz FS of 2s period as repeated intermittently at every 15s for over the period of 2, 10, and 30min were much less effective for increasing plasma VP, whereas these intermittent FS increased plasma ACTH to an extremely high level. During the inter-shock intervals of 13s between successive two shock periods rats exhibited a "freezing" behavior. Hypertonic saline or urethane injected I.P, immediately after termination of the intermittent FS significantly increased VP as well as ACTH in the plasma. These data clearly indicate that FS potentiate VP secretion and suggest the possibility that emotional stress may suppress the noxious stimuli-induced VP secretion.

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The possibility that emotional stress suppresses footshock-induced, secretion of antidiuretic hormone (VP) was tested in rats by a classical conditioning paradigm. As a training trial, rats received a flash and a brief sound (2kHz, 0.5s) as conditioned stimuli (CS) followed by footshocks (FS, 5ms pulses of 3mA intensity, 50Hz) for 1s period as unconditioned stimuli. Rats were trained by 100 trials repeated at an interval of 6s. A various length of time after the training, rats were tested by CS repeated at an interval of 15s for the period of 120s and FS of 60s period, which started 60s after the CS onset. Testing CS further augmented FS-induced increase in plasma adrenocorticotrophic hormone (ACTH) but suppressed FS-induced increase in plasma VP in a time-dependent manner. The CS also increased the degree of an inhibition of motor behavior known as "freezing" behavior. Augmentation of ACTH response and suppression of VP response to testing FS were dependent on the training shock intensity. These data are consistent with the hypothesis that VP secretion is potentiated by physical but suppressed by emotional stress.

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The present study was undertaken to measure tissue contents of Na, Li, and Cl non-invasively in the isolated perfused organ by nuclear magnetic resonance (NMR) using a broadband tunable probe. The NMR signals of ²³Na, ⁷Li, and ³⁵Cl from the isolated perfused rat mandibular gland were collected continuously and each spectrum was obtained for every 15 or 20s. The Na concentration in the perfusate was varied by replacement with Li, and the resulting changes were monitored by measuring the signal intensities of the electrolytes. The time constant for Na exchange was slower following complete removal of extracellular Na than following its half replacement, suggesting that the Na extrusion by Na⁺/K⁺ ATPase was reduced by lowering the extracellular Na level. The time constant for Li exchange was slower than that .for Na exchange. The level of Cl was nearly constant during experiment, except for a very slow increase in Cl, possibly resulting from increasing edema and/or intracellular Li storage.

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We considered the possible relationship between the serum levels of progesterone and estradiol-17β, which were controlled to that of several stages in normal pregnant rats, and the Ca²⁺ sensitivity, defined as the pCa required for half maximum activation of force production, of chemically skinned uterine muscle fibers from ovariectomized rats. The Ca²⁺ sensitivity was negligibly influenced by the levels of these hormones.

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