Journal of Physiological Sciences最新文献

Na⁺/Mg²⁺ exchange transport, the Na⁺ gradient-driven Mg²⁺ extrusion system, plays a key role in cellular Mg²⁺ homeostasis. To date, the molecular entity and selective inhibitors of Na⁺/Mg²⁺ exchanger have not been fully explored. Intracellular free Mg²⁺ concentration ([Mg²⁺]_i) was measured in ventricular myocytes acutely isolated from rat hearts. After soaking the cells in high-Mg²⁺ low-Na⁺ solution to increase [Mg²⁺]_i, the addition of extracellular Na⁺ caused a decrease in [Mg²⁺]_i. We analyzed the rate of decrease in [Mg²⁺]_i as Na⁺/Mg²⁺ exchange transport activity. The suppression of the rate of decrease in [Mg²⁺]_i caused by sertraline, a selective serotonin reuptake inhibitor (SSRI), was concentration dependent (IC₅₀ 8.9 μM) and reversible. Other SSRIs, namely paroxetine and fluvoxamine, were less effective than sertraline. In conclusion, sertraline inhibited Na⁺/Mg²⁺ exchange transport more effectively than any previously reported inhibitors of Na⁺/Mg²⁺ exchanger. Sertraline could be used as a tool to characterize the functions of Na⁺/Mg²⁺ exchanger.

The aim of the present study was to examine C-fiber-related brain responses evoked by laser heat stimuli applied to the lumbar area, and to determine the stimulation protocol that produces the most reliable responses. Thirty healthy volunteers completed the study. Combinations of different stimuli (single pulses or trains of three pulses) with different pulse durations (7 or 14 ms) were used to compare C-fiber-related brain responses between protocols. The four protocols elicited comparable C-fiber-related brain responses to laser heat pulses. However, pulse trains of 7 ms pulses at 0.67 Hz elicited C-LEPs in the greatest proportion of participants (86.7 %). C-LEPs occurred within a 500 ms to 1500 ms post-stimulus time window, consistent with the perception associated with C-fiber activation. These results provide novel data on C-fiber-related brain responses to painful stimuli and a reliable stimulation protocol for future studies on low back pain.

Aging is understood to be a time-dependent decline in various physiological functions. Motor and sensory functions deteriorate relatively early after maturity, while nutrient absorption and barrier functions in the digestive tract are reported to decline later, but the specific sites and mechanisms remain unclear. Senescence-Accelerated Mouse Prone 1 (SAMP1) mice (9 months) and C57BL/6 mice (over 19 months) were used to examine age-related changes in intestinal function of different regions using Ussing chambers. In SAMP1 mice, nutrient absorption and tight junction cationic permeability were reduced, while barrier function was enhanced in the middle and distal small intestine. Similar functional declines were observed in the distal small intestine of aged C57BL/6 mice. These findings suggest that the effect of aging is first observed in the distal small intestine, and that cation selectivity of the epithelial intercellular tight junction could serve as a new indicator for aging and functional evaluation index.

Blood flow restricted (BFR) exercise induces musculoskeletal adaptations at reduced exercise loads. The role of hypercapnia during BFR remains unclear, due to difficulties in isolating this factor in vivo. We evaluated a hypercapnic model designed to raise CO₂ levels similar to low-intensity exercise, while minimizing other exercise-induced effects (e.g. hypoxia, lactate accumulation). In a crossover design, 18 participants were administered pure CO₂ (EXP) or room air (CON) transcutaneously from the neck down for 90 min. Ventilatory and blood markers (V̇CO₂, ETCO₂, V̇E, pH, and PCO₂) were measured throughout. The area under the curve of ETCO₂ was higher during EXP compared to CON (75.5 ± 83.7 vs. 32.8 ± 57.5 a.u., p = 0.05), confirming successful CO₂ administration. However, there was no significant effect on PCO₂ (p = 0.09), despite a trend toward reduced pH (p = 0.059). CONCLUSION: While transcutaneous CO₂ absorption induced a physiological response, the magnitude was small, and this model shows limited ecological validity to simulate exercise-like conditions.

The role of calcium release-activated calcium channel (CRAC) inhibitors in the pathogenesis of rheumatoid arthritis (RA) is unclear. We focused on stromal interaction molecule 1 (STIM1) and Ca²⁺ release-activated channel regulator 2 A (CRACR2A), which participate in CRAC activation, to understand the signaling mechanism of human RA fibroblast-like synovial (FLS) cells in response to shear stress (SS). Human normal and RA FLS cell cultures were studied. The rates of intracellular calcium release and extracellular calcium influx in response to SS differed, and the responses to the first and second stimuli were analyzed. In the RA FLS cells, CRAC inhibitor significantly decreased the second/first stimulus ratio compared with that of the normal cells, and STIM1 and CRACR2A exhibited significantly increased expression levels compared with those in the normal FLS cells. Therefore, STIM1 and CRACR2A expression and Ca²⁺ influx in FLS cells are implicated in the pathogenesis of RA.

The aim of the present study was to examine the contribution of spinal and supraspinal processes to pain modulation by attention. It is hypothesized that pain inhibition by distraction is accompanied by reduced pain-evoked pupil dilation and cerebral activity, but no inhibition of the nociceptive flexion reflex (NFR), while pain anticipation is expected to increase pain perception and pain-related responses. Twenty healthy volunteers received 90 painful stimuli in control, distraction (mental arithmetic), and anticipation (visual cue) conditions. Anticipation did not modulate pain (p = .7), while distraction decreased pain significantly (p < .001). Moreover, pupil diameter increased 500-1000 ms post-stimulus in the control condition (p < .05), but this response was abolished by distraction. Distraction also decreased pain-related brain activity (high-gamma oscillations) (p = .004), but not the NFR (p = .3). These results suggest that pain inhibition by distraction is produced, in part, by supraspinal inhibition of nociceptive processes.

Orofacial temperature influences orofacial functions and is related to hemodynamics mediated by the autonomic nerves. Although the properties of autonomic vasomotor responses differ in orofacial tissues, differences in the autonomic regulation of orofacial temperature are unclear. We examined the differences in blood flow (BF) and temperature (Tm) between the extraoral (lower lip) and intraoral tissues (tongue) of urethane-anesthetized rats. Noncholinergic parasympathetic vasodilation evoked by trigeminal-mediated reflex elicited significant increases in BF and Tm in both tissues, and these increases were larger in the tongue than in the lower lip. Activation of cervical sympathetic nerves significantly decreased BF and Tm in both tissues. These decreases were restored by parasympathetic reflex vasodilation; the effects were larger in the tongue than in the lower lip. Our results suggest that parasympathetic vasodilation is involved in the maintenance of BF and Tm, and that the effects may be greater in intraoral than in extraoral tissues.

This study aimed to investigate the influence of aging on steroid hormone production in skeletal muscles in response to resistance training. Male F344 rats, aged 4 months (young) and 22 months (old), were randomized into the sedentary and training groups. The training group performed resistance training by climbing a ladder with a load every three days for eight weeks. After the training period, the flexor hallucis longus muscle was dissection, and muscle steroid hormone levels were analyzed using liquid chromatography-tandem mass spectrometry. We found that resistance training significantly increased muscle mass in young and old rats, although the increase was less pronounced in the latter. In young, trained rats, muscle dihydrotestosterone levels were approximately 35-fold higher compared to sedentary controls (p < 0.01); dihydrotestosterone levels did not differ significantly between sedentary and trained old rats. These findings indicate that resistance training-induced dihydrotestosterone production is blunted in aging rat skeletal muscle.

In humans, loss-of-function mutations in multiple component genes of transforming growth factor (TGF)-β signaling have been demonstrated to cause proximal aortic aneurysms. However, association of human variants in the prototype ligand TGFB1 with thoracic aortic aneurysms have not been reported to date. To delineate the consequences of genetically altered Tgfb1 expression on aortic phenotype in mammals, we studied aortic phenotype in mice with loss-of-functions or gain-of-function mutations in Tgfb1 (Tgfb1^L/L and Tgfb1^H/H). Tgfb1^L/L mice spontaneously developed proximal aortic aneurysms and had markedly shortened lifespans as compared with wildtype, whereas Tgfb1^H/Hmice did not develop aortic aneurysms and had comparable lifespans with wildtype. Aortic levels of collagen and elastin stable crosslinks, and the expression of their associated enzymes in Tgfb1^L/L mice were significantly less than those in wildtype. These results suggest that TGF-β1 is protective against aortic aneurysms at least partly via increasing the cross-linking of collagen and elastin.

The capsaicin receptor TRPV1 was identified as the first heat-activated ion channel in 1997. Since then, numerous studies have been performed on its physiological functions and structure-function relationship, and chemicals targeting TRPV1 have been developed. It has been more than 27 years since the initial cloning of the TRPV1 gene and more than 11 years since the clarification of its structure at the atomic level using cryo-EM. However, we still lack good chemical antagonists of TRPV1 as medicines. TRPV1 is involved in body temperature regulation, but how TRPV1 antagonists cause hyperthermia and how TRPV1 is involved in body temperature regulation are not yet clearly understood. More research is needed in the thermal biology field.