The intracellular signaling pathways responsible for extracellualr uridine-5'-triphosphate (UTP_o)-induced chloride (Cl⁻) currents (I_Cl.UTP) were studied in mouse ventricular myocytes with the whole-cell clamp technique. UTP_o (0.1 to 100 μM) activated a whole-cell current that showed a time-independent activation, a linear current-voltage relationship in symmetrical Cl⁻ solutions, an anion selectivity of Cl⁻ > iodide > aspartate, and an inhibition by a thiazolidinone-derived specific inhibitor (CFTR_inh-172, 10 μM) of cystic fibrosis transmembrane conductance regulator (CFTR), but not by a disulfonic stilbene derivative (DIDS, 100 μM), these properties matching those of CFTR Cl⁻ channels. The potency order of nucleotides for an activation of the Cl⁻ current was UTP = ATP > uridine-5'-diphosphate (UDP) = ADP. Suramin (100 μM), a P2Y receptor antagonist, strongly inhibited the UTP_o-activation of the Cl⁻ current, whereas pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS, 100 μM), another P2Y receptor antagonist, induced little inhibition of I_Cl.UTP. The activation of I_Cl.UTP was sensitive to protein kinase C (PKC) inhibitor, phospholipase C (PLC) inhibitor, intracellular GDPβS (nonhydrolyzable GDP analogue) or anti-Gq/11 antibody. UTP_o failed to activate the Cl⁻ current when the cells were dialyzed with nonhydrolyzable ATP analogues (ATPS or AMP-PNP) without ATP, suggesting that ATP hydrolysis is a prerequisite for the current activation. I_Cl.UTP was persistently activated with a mixture of ATPγS + ATP in the pipette, suggesting the involvement of phosphorylation reaction in the current activation process. Our results strongly suggest that I_Cl.UTP is due to the activation of CFTR Cl⁻ channels through Gq/11-coupled P2Y₂ receptor-PLC-PKC signaling and ATP hydrolysis in mouse heart.

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Previous studies have shown that plasma volume (PV) loss can be a confounding variable in the interpretation of changes in blood constituents. We examined the effect of PV loss on three features of the blood lactate versus work-rate relationship, namely, slight blood lactate increase during the early stages of graded exercise testing (GXT); work rate at the onset of a systematic increase in blood lactate, i.e., lactate threshold (LT); and work rate at a blood lactate concentration of 4 mM, i.e., onset of blood lactate accumulation (OBLA). Fourteen subjects underwent cycle ergometer GXT. Blood samples were obtained at rest and at the end of each 3-min work-rate increment and analyzed for hematocrit and lactate concentration. For exercise levels up to and including LT, PV loss was relatively stable at approximately 2.8%. Beyond LT, PV loss accelerated. From the first work rate to LT, blood lactate concentration uncorrected for PV loss increased 0.24 ± 0.07 mM (P < 0.05). After correction for PV loss, the increase was 0.21 ± 0.08 mM (P < 0.05). These mean increases were not significantly different from each other. For the four exercise levels above LT common to most subjects, PV-corrected lactate values were significantly lower than uncorrected values. Correction of lactate values for PV loss did not alter LT for any subject, but it did result in a significant increase in OBLA. Thus, PV loss has the potential to be a confounding variable for the interpretation of blood lactate parameters that are determined at exercise levels above LT.

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Serum concentrations of urea and cholesterol were used as indicators of liver function in rabbits in an investigation of the responsiveness of the daily rhythm of liver function to phase shifts in the environmental light-dark cycle. Locomotor activity was simultaneously monitored by actigraphy. Serum urea and cholesterol concentrations exhibited robust daily rhythmicity with opposite phases. Both indicators of liver function phase shifted in response to phase shifts of the light-dark cycle. The phase shifts in liver function appeared to be parallel to phase shifts in locomotor activity, but the data were not sufficiently strong to confirm that the liver relies on the secondary effect of photic phase shift on ingestive behavior in order to be phase-shifted by light as previously indicated by gene expression studies in laboratory rodents.

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We have reported that after rats were acclimated to heat for about 5 h daily at a fixed time, the pattern of day-night variations of core temperature (T_cor) altered, i.e., their T_cor fell, especially during the period when they had previously been exposed to heat. The suprachiasmatic nucleus (SCN) of the hypothalamus is known to be indispensable for the genesis of circadian rhythms of T_cor. We therefore investigated the involvement of the SCN in the characteristic fall in T_cor in heat-acclimated rats. The rats were exposed to an ambient temperature of 33°C only in the last half of the dark phase for 10 consecutive days. After the heat exposure schedule, the nocturnal pattern of T_cor variations and Fos expression in the dorsomedial SCN altered so that the T_cor and the number of Fos immunoreactive cells decreased in the last half of the dark phase. The bilateral lesions of the SCN of rats were made electrically, and the electrical lesions of the SCNs abolished the daily cycle of T_cor. In the SCN-lesioned rats, theT_cor levels were significantly lowered after the 10-day heat exposure schedule. However, their T_cor did not specifically drop during the period when they had previously been exposed to heat. These findings suggest that the SCN is crucial for establishing a time memory for heat stress, and it plays a minimal role in heat acclimation-induced changes in T_cor in rats.

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Acupuncture points (APs) are well known to be small regions of local or referred pain that are more sensitive than surrounding tissue. Based on bibliographical and clinical data, specific conditions are commonly believed to change the pain sensitivity at corresponding APs. The aim of the present study was to investigate whether the pressure pain threshold (PPT) of specific APs is associated with the severity of premenstrual syndrome. The 46 participants were female students attending a middle school. Premenstrual syndrome (PMS) was measured using a structured questionnaire, the menstruation distress questionnaire (MDQ). High PMS (HP) and low PMS (LP) groups were divided based on their MDQ scores. The PPTs at sites in the leg (the APs SP6, GB39, and LR3 and a non-AP 2-cm anterior to SP6) and in the arm (the APs PC6, TE5, and LI4 and a non-AP 2-cm proximal to PC6) were measured using an algometer. The PPT of the HP group at SP6 was significantly lower than that of the LP group (13.50 ± 0.73 vs. 16.30 ± 0.66 kilopascals, P < 0.05), but not at other APs or at non-APs. The findings of our study support the hypothesis that the alteration of pain threshold at specific APs is associated with the severity of corresponding diseases. Further studies are needed to determine whether an observation of pain sensitivity at the APs could be used as an adjunctive tool for the diagnosis of a clinical problem.

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In this study, we focused on two types of perspiration, one triggered by anticipatory anxiety and the other by voluntary deep inspiration. We have previously found that the anticipation of anxiety causes increases of respiratory frequency, and that these increases are related to an activation of the temporal pole and amygdala in humans. Our interest is in the difference between the two natures of perspiration, both of which are closely related to respiratory responses. The level of sweating responses did not differ between deep and active inspiration or between three trials. This means that there was no habituation with repetitive trials for voluntary breathing. On the other hand, sweating responses during anticipation of anxiety showed habituation with repetitive trials. Habituation and nonhabituation differences with respect to these two characteristics of perspiration could be the result of differences in the related central networks. The former might be involved cortical structures associated with conscious changes of respiration. The latter was induced unconsciously, and this unconscious response is similar to the respiratory response during anticipatory anxiety, which may be related to the activation of the limbic system. Further, there was a positive correlation found between the amount of perspiration response and the state anxiety scores in deep inspiration, and also in trial 1 of the anticipatory anxiety experiment. Both types of responses were related to the individual state anxiety scores, and this may contribute to the defense mechanism with regard to adjustments to changes in the outer environment and situations.

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The role of the serratus anterior (SA) as an accessory muscle of ventilation and its physiologic significance under exercising conditions remains unclear. Recent investigations have utilized the measurement of SA as an analog for respiratory muscle oxygenation. The purpose of this investigation was to examine the action of the serratus anterior via surface electromyography (EMG) and near infrared spectroscopy (NIRS) during exercise while controlling for muscular effort not related to ventilation. Nine healthy volunteers (age = 24.4 ± 0.5 years, VO_2max= 3.416 ± 0.35 l min⁻¹; V_Epeak = 127.5 ± 13.1 l min⁻¹; TV_peak = 2.844 ± 0.226 l) completed a graded exercise test to volitional exhaustion on a cycle ergometer. The subjects’ arms were folded and relaxed at the abdomen to minimize muscular effort resulting from scapular stabilization during pushing/forward flexion of the arms associated with cycle ergometry. VO₂ and V_E were monitored breath-by-breath throughout exercise. EMG was recorded over the right SA, and a near infrared probe was placed over the left SA. No significant differences were observed throughout the graded exercise test for tissue oxygenation (StO₂) (n = 6, F[1.532, 7.661] = 0.895, P > 0.05, η² = 0.15) or EMG (n = 9, F[1.594, 12.75] = 3.067, P > 0.05, η² = 0.27). Although the recruitment of the SA has been postulated to aid in ventilation in various postures and disease states, it is concluded that it shows little muscular effort in healthy subjects during upright cycling. Additional research is needed to conclude the pertinence of utilizing StO₂ of the SA as an analog for respiratory muscle oxygenation.

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Hyperbaric exposure with high oxygen concentration inhibits a growth-related increase in the glucose and insulin of diabetic rats. In this study, 5-week-old diabetic Goto-Kakizaki rats were exposed to a hyperbaric environment (1.25 atmospheric pressure) with a high oxygen concentration (36%) for 6 h daily. Fiber type distributions and oxidative enzyme activities in the fast-twitch plantaris muscle of Goto-Kakizaki rats were examined after hyperbaric exposure for 4 weeks. The percentages of high-oxidative type I and type IIA fibers increased and that of low-oxidative type IIB fibers decreased after hyperbaric exposure. Furthermore, the fiber oxidative enzyme activity increased after hyperbaric exposure, regardless of fiber type. It is concluded that altered patterns of fiber types in the plantaris muscle of diabetic rats shift toward normal, which is observed in nondiabetic rats, following hyperbaric exposure with high oxygen concentration.

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