Ph.D., The University of Electro-Communications, Mar. 2023

Life sciences, Sports science

Life sciences, Physiology

Apr. 2023 - Present
The University of Electro-Communications, Graduate School of Informatics and Engineering, 助教

Apr. 2021 - Mar. 2023
独立行政法人 日本学術振興会 特別研究員 （DC2）

Jun. 2020 - Mar. 2023
The University of Electro-Communications, Center For Neuroscience And Biomedical Engineering, 事務補佐員

Apr. 2020 - Mar. 2023
The University of Electro-Communications, Graduate School of Informatics and Engineering, Department of Engineering Science

Apr. 2018 - Mar. 2020
The University of Electro-Communications, Graduate School of Informatics and Engineering, 基盤理工学専攻 博士前期課程

Apr. 2014 - Mar. 2018
The University of Electro-Communications, 情報理工学部, 先進理工学科

Aug. 2023
一般社団法人 日本体力医学会
Pharmacological Inhibition of Ryanodine Receptors Immediately After Eccentric Contractions Exercise Effectively Reduces Exercise-induced Muscle Damage In Rat Skeletal Muscle
2023 International Academic Exchange Best Oral Award

May 2023
学術変革領域研究（A）「散乱透視学」
高速PLC-DHMによる哺乳類骨格筋細胞の観察
優秀ポスター講演賞

Mar. 2020
電気通信大学
目黒会賞

In vivo heat production dynamics during a contraction-relaxation cycle in rat single skeletal muscle fibers.
Ayaka Tabuchi; Yoshinori Tanaka; Hiroshi Horikawa; Takuto Tazawa; David C Poole; Yutaka Kano
Lead, Journal of thermal biology, 119, 103760-103760, 30 Nov. 2023, Peer-reviwed, True, Skeletal muscle generates heat via contraction-dependent (shivering) and independent (nonshivering) mechanisms. While this thermogenic capacity of skeletal muscle undoubtedly contributes to the body temperature homeostasis of animals and impacts various cellular functions, the intracellular temperature and its dynamics in skeletal muscle in vivo remain elusive. We aimed to determine the intracellular temperature and its changes within skeletal muscle in vivo during contraction and following relaxation. In addition, we tested the hypothesis that sarcoplasmic reticulum Ca2+ ATPase (SERCA) generates heat and increases the myocyte temperature during a transitory Ca2+-induced contraction-relaxation cycle. The intact spinotrapezius muscle of anesthetized adult male Wistar rats (n = 18) was exteriorized and loaded with the fluorescent probe Cellular Thermoprobe for Fluorescence Ratio (49.3 μM) by microinjection over 1 s. The fluorescence ratio (i.e., 580 nm/515 nm) was measured in vivo during 1) temperature increases induced by means of an external heater, and 2) Ca2+ injection (3.9 nL, 2.0 mM). The fluorescence ratio increased as a linear function of muscle surface temperature from 25 °C to 40 °C (r2 = 0.97, P < 0.01). Ca2+ injection (3.9 nL, 2.0 mM) significantly increased myocyte intracellular temperature: An effect that was suppressed by SERCA inhibition with cyclopiazonic acid (CPA, Ca2+: 38.3 ± 1.4 °C vs Ca2++CPA: 28.3 ± 2.8 °C, P < 0.01 at 1 min following injection). While muscle shortening occurred immediately after the Ca2+ injection, the increased muscle temperature was maintained during the relaxation phase. In this investigation, we demonstrated a novel model for measuring the intracellular temperature of skeletal muscle in vivo and further that heat generation occurs concomitant principally with SERCA functioning and muscle relaxation.
Scientific journal, English

Cmah deficiency blunts cellular senescence in adipose tissues and improves whole-body glucose metabolism in aged mice.
Reo Takeda; Ayaka Tabuchi; Yudai Nonaka; Ryotaro Kano; Mizuki Sudo; Yutaka Kano; Daisuke Hoshino
Geriatrics & gerontology international, 15 Nov. 2023, Peer-reviwed, False, AIM: Cytidine monophosphate-N-acetylneuraminic acid (Neu5Ac) hydroxylase (Cmah) is an enzyme, which converts Neu5Ac to the sialic acid Neu5Gc. Neu5Gc is thought to increase inflammatory cytokines, which are, in part, produced in senescent cells of adipose tissues. Cellular senescence in adipose tissues induces whole-body aging and impaired glucose metabolism. Therefore, we hypothesized that Cmah deficiency would prevent cellular senescence in adipose tissues and impaired glucose metabolism. METHODS: Wild-type (WT) and Cmah knockout (KO) mice aged 24-25 months were used. Whole-body metabolism was assessed using a metabolic gas analysis system. We measured blood glucose and insulin concentrations after oral glucose administration. The size of the lipid droplets in the liver was quantified. Markers of cellular senescence and senescence-associated secretory phenotypes were measured in adipose tissues. RESULTS: Cmah KO had significantly increased VO2 and energy expenditure (P < 0.01). Unlike glucose, the insulin concentration after oral glucose administration was significantly lower in the Cmah KO group than in the WT group (P < 0.001). Lipid droplets in the liver were significantly lower in the Cmah KO group than in the WT group (P < 0.05). The markers of cellular senescence and senescence-associated secretory phenotypes in the adipose tissues were significantly lower in the Cmah KO group than in the WT group (P < 0.05). CONCLUSIONS: Cmah deficiency blunted cellular senescence in adipose tissues and improved whole-body glucose metabolism. These characteristics in aged Cmah KO mice might be associated with higher energy expenditure. Geriatr Gerontol Int 2023; ••: ••-••.
Scientific journal, English

In vivo cytosolic H2O2 changes and Ca2+ homeostasis in mouse skeletal muscle.
Ryotaro Kano; Ayaka Tabuchi; Yoshinori Tanaka; Hideki Shirakawa; Daisuke Hoshino; David C Poole; Yutaka Kano
American journal of physiology. Regulatory, integrative and comparative physiology, 30 Oct. 2023, Peer-reviwed, True, Hydrogen peroxide (H2O2) and calcium ions (Ca2+) are functional regulators of skeletal muscle contraction and metabolism. Although H2O2 is one of the activators of the type-1 ryanodine receptor (RyR1) in the Ca2+ release channel, the interdependence between H2O2 and Ca2+ dynamics remains unclear. This study tested the following hypotheses using an in vivo model of mouse tibialis anterior (TA) skeletal muscle. 1. Under resting conditions, elevated cytosolic H2O2 concentration ([H2O2]cyto) leads to a concentration-dependent increase in cytosolic Ca2+concentration ([Ca2+]cyto) through its effect on RyR1. 2. In hypoxia (cardiac arrest) and muscle contractions (electrical stimulation), increased [H2O2]cyto induce Ca2+ accumulation. Cytosolic H2O2 (HyPer7) and Ca2+ (Fura-2) dynamics were resolved by TA bioimaging in C57BL/6J male mice under four conditions: Elevated exogenous H2O2, Cardiac arrest, Twitch and Tetanic contractions. Exogenous H2O2 (0.1-100mM) induced a concentration-dependent increase in [H2O2]cyto (+55%,0.1mM; +280%,100mM) and an increase in [Ca2+]cyto (+3%,1.0mM; +8%,10mM). This increase in [Ca2+]cyto was inhibited by pharmacological inhibition of RyR1 by dantrolene. Cardiac arrest-induced hypoxia increased [H2O2]cyto (+33%) and [Ca2+]cyto (+20%) 50min post-cardiac arrest. Compared to exogenous 1.0mM H2O2 condition, [H2O2]cyto after tetanic contractions rose less than one-tenth as much, while [Ca2+]cyto was 4.7-fold higher. In conclusion, substantial increases in [H2O2]cyto levels evoke only modest Ca2+ accumulation via their effect on the sarcoplasmic reticulum RyR1. On the other hand, contrary to hypoxia secondary to cardiac arrest, increases in [H2O2]cyto from contractions are small, indicating that H2O2 generation is unlikely to be a primary factor driving the significant Ca2+ accumulation after, especially tetanic, muscle contractions.
Scientific journal, English

The aminopeptidase LAP3 suppression accelerates myogenic differentiation via the AKT-TFE3 pathway in C2C12 myoblasts.
Shion Osana; Yasuo Kitajima; Suzuki Naoki; Kazutaka Murayama; Hiroaki Takada; Ayaka Tabuchi; Yutaka Kano; Ryoichi Nagatomi
Journal of cellular physiology, 12 Jul. 2023, Peer-reviwed, True, Skeletal muscle maintenance depends largely on muscle stem cells (satellite cells) that supply myoblasts required for muscle regeneration and growth. The ubiquitin-proteasome system is the major intracellular protein degradation pathway. We previously reported that proteasome dysfunction in skeletal muscle significantly impairs muscle growth and development. Furthermore, the inhibition of aminopeptidase, a proteolytic enzyme that removes amino acids from the termini of peptides derived from proteasomal proteolysis, impairs the proliferation and differentiation ability of C2C12 myoblasts. However, no evidence has been reported on the role of aminopeptidases with different substrate specificities on myogenesis. In this study, therefore, we investigated whether the knockdown of aminopeptidases in differentiating C2C12 myoblasts affects myogenesis. The knockdown of the X-prolyl aminopeptidase 1, aspartyl aminopeptidase, leucyl-cystinyl aminopeptidase, methionyl aminopeptidase 1, methionyl aminopeptidase 2, puromycine-sensitive aminopeptidase, and arginyl aminopeptidase like 1 gene in C2C12 myoblasts resulted in defective myogenic differentiation. Surprisingly, the knockdown of leucine aminopeptidase 3 (LAP3) in C2C12 myoblasts promoted myogenic differentiation. We also found that suppression of LAP3 expression in C2C12 myoblasts resulted in the inhibition of proteasomal proteolysis, decreased intracellular branched-chain amino acid levels, and enhanced mTORC2-mediated AKT phosphorylation (S473). Furthermore, phosphorylated AKT induced the translocation of TFE3 from the nucleus to the cytoplasm, promoting myogenic differentiation through increased expression of myogenin. Overall, our study highlights the association of aminopeptidases with myogenic differentiation.
Scientific journal, English

Chronic repetitive cooling and caffeine-induced intracellular Ca²⁺ elevation differentially impact adaptations in slow- and fast-twitch rat skeletal muscles
Ryo Takagi; Ayaka Tabuchi; Kosei Hayakawa; Shion Osana; Hiroya Yabuta; Daisuke Hoshino; David C. Poole; Yutaka Kano
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, American Physiological Society, 19 Jun. 2023, Peer-reviwed, Intracellular Ca²⁺ concentration ([Ca²⁺]i) is considered important in the regulation of skeletal muscle mass. This study tested the hypothesis that chronic repeated cooling and/or caffeine ingestion would acutely increase [Ca²⁺]i and hypertrophy muscles potentially in a fiber type-dependent manner. Control rats and those fed caffeine, were subjected to repeated bidiurnal treatments of percutaneous icing, under anaesthesia, to reduce the muscle temperature below ~5°C. The predominantly fast twitch tibialis anterior (TA) and slow twitch soleus (SOL) muscles were evaluated after 28 days intervention. The [Ca²⁺]i elevating response to icing was enhanced by caffeine loading only in the SOL muscle, with the response present across a significantly higher temperature range than in the TA muscle under caffeine loading conditions. In both the TA and SOL muscles, myofiber cross-sectional area (CSA) was decreased by chronic caffeine treatment (mean reductions of 10.5% and 20.4%, respectively). However, in the TA , but not the SOL, CSA was restored by icing (+15.4 ± 4.3% vs. non-iced, P<0.01). In the SOL but not TA, icing+caffeine increased myofiber number (20.5 ± 6.7%, P<0.05) and satellite cell density (2.5 ± 0.3-fold) in cross sections. These contrasting muscle responses to cooling and caffeine may reflect fiber-type specific [Ca²⁺]i responses and/or differential responses to elevated [Ca²⁺]i.
Scientific journal

Ryanodine receptors mediate high intracellular Ca2+ and some myocyte damage following eccentric contractions in rat fast-twitch skeletal muscle.
Ayaka Tabuchi; Yoshinori Tanaka; Ryo Takagi; Hideki Shirakawa; Tsubasa Shibaguchi; Takao Sugiura; David C Poole; Yutaka Kano
Lead, American journal of physiology. Regulatory, integrative and comparative physiology, 322, 1, R14-R27, 01 Jan. 2022, Peer-reviwed, True, Eccentric contractions (ECC) facilitate cytosolic calcium ion (Ca2+) release from the sarcoplasmic reticulum (SR) and Ca2+ influx from the extracellular space. Ca2+ is a vital signaling messenger that regulates multiple cellular processes via its spatial and temporal concentration ([Ca2+]i) dynamics. We hypothesized that 1) a specific pattern of spatial/temporal intramyocyte Ca2+ dynamics portends muscle damage following ECC and 2) these dynamics would be regulated by the ryanodine receptor (RyR). [Ca2+]i in the tibialis anterior muscles of anesthetized adult Wistar rats was measured by ratiometric (i.e., ratio, R, 340/380 nm excitation) in vivo bioimaging with Fura-2 pre-ECC and at 5 and 24 h post-ECC (5 × 40 contractions). Separate groups of rats received RyR inhibitor dantrolene (DAN; 10 mg/kg ip) immediately post-ECC (+DAN). Muscle damage was evaluated by histological analysis on hematoxylin-eosin stained muscle sections. Compared with control (CONT, no ECC), [Ca2+]i distribution was heterogeneous with increased percent total area of high [Ca2+]i sites (operationally defined as R ≥ 1.39, i.e., ≥1 SD of mean control) 5 h post-ECC (CONT, 14.0 ± 8.0; ECC5h: 52.0 ± 7.4%, P < 0.01). DAN substantially reduced the high [Ca2+]i area 5 h post-ECC (ECC5h + DAN: 6.4 ± 3.1%, P < 0.01) and myocyte damage (ECC24h, 63.2 ± 1.0%; ECC24h + DAN: 29.1 ± 2.2%, P < 0.01). Temporal and spatially amplified [Ca2+]i fluctuations occurred regardless of DAN (ECC vs. ECC + DAN, P > 0.05). These results suggest that the RyR-mediated local high [Ca2+]i itself is related to the magnitude of muscle damage, whereas the [Ca2+]i fluctuation is an RyR-independent phenomenon.
Scientific journal, English

In vivo cooling-induced intracellular Ca2+ elevation and tension in rat skeletal muscle.
Ryo Takagi; Ayaka Tabuchi; David C Poole; Yutaka Kano
Physiological reports, 9, 13, e14921, Jul. 2021, Peer-reviwed, True, It is an open question as to whether cooling-induced muscle contraction occurs in the in vivo environment. In this investigation, we tested the hypotheses that a rise in intracellular Ca²⁺ concentration ([Ca²⁺]i) and concomitant muscle contraction could be evoked in vivo by reducing muscle temperature and that this phenomenon would be facilitated or inhibited by specific pharmacological interventions designed to impact Ca²⁺-induced Ca²⁺-release (CICR). Progressive temperature reductions were imposed on the spinotrapezius muscle of Wistar rats under isoflurane anesthesia by means of cold fluid immersion. The magnitude, location, and temporal profile of [Ca²⁺]i were estimated using fura-2 loading. Caffeine (1.25-5.0 mM) and procaine (1.6-25.6 mM) loading were applied in separatum to evaluate response plasticity by promoting or inhibiting CICR, respectively. Lowering the temperature of the muscle surface to ~5°C produced active tension and discrete sites with elevated [Ca²⁺]i. This [Ca²⁺]i elevation differed in magnitude from fiber to fiber and also from site to site within a fiber. Caffeine at 1.25 and 5.0 mM reduced the magnitude of cooling necessary to elevate [Ca²⁺]i (i.e., from ~5°C to ~8 and ~16°C, respectively, both p < 0.05) and tension. Conversely, 25.6 mM procaine lowered the temperature at which [Ca²⁺]i elevation and tension were detected to ~2°C (p < 0.05). Herein we demonstrate the spatial and temporal relationship between cooling-induced [Ca²⁺]i elevation and muscle contractile force in vivo and the plasticity of these responses with CICR promotion and inhibition.
Scientific journal, English

Vascular permeability of skeletal muscle microvessels in rat arterial ligation model: in vivo analysis using two-photon laser scanning microscopy.
Rie Shimotsu; Kzuki Hotta; Ryo Ikegami; Tomoyo Asamura; Ayaka Tabuchi; Kazuto Masamoto; Kazuyoshi Yagishita; David C Poole; Yutaka Kano
American journal of physiology. Regulatory, integrative and comparative physiology, 320, 6, R972-R983, 01 Jun. 2021, Peer-reviwed, True, Peripheral artery disease (PAD) in the lower limb compromises oxygen supply due to arterial occlusion. Ischemic skeletal muscle is accompanied by capillary structural deformation. Therefore, using novel microscopy techniques, we tested the hypothesis that endothelial cell swelling temporally and quantitatively corresponds to enhanced microvascular permeability. Hindlimb ischemia was created in male Wistar rat's by iliac artery ligation (AL). The tibialis anterior (TA) muscle microcirculation was imaged using intravenously infused rhodamine B isothiocyanate dextran fluorescent dye via two-photon laser scanning microscopy (TPLSM) and dye extravasation at 3 and 7 days post-AL quantified to assess microvascular permeability. The TA microvascular endothelial ultrastructure was analyzed by transmission electron microscopy (TEM). Compared with control (0.40 ± 0.15 μm3 × 106), using TPLSM, the volumetrically determined interstitial leakage of fluorescent dye measured at 3 (3.0 ± 0.40 μm3 × 106) and 7 (2.5 ± 0.8 μm3 × 106) days was increased (both P < 0.05). Capillary wall thickness was also elevated at 3 (0.21 ± 0.06 μm) and 7 (0.21 ± 0.08 μm) days versus control (0.11 ± 0.03 μm, both P < 0.05). Capillary endothelial cell swelling was temporally and quantitatively associated with elevated vascular permeability in the AL model of PAD but these changes occurred in the absence of elevations in protein levels of vascular endothelial growth factor (VEGF) its receptor (VEGFR2 which decreased by AL-7 day) or matrix metalloproteinase. The temporal coherence of endothelial cell swelling and increased vascular permeability supports a common upstream mediator. TPLSM, in combination with TEM, provides a sensitive and spatially discrete technique to assess the mechanistic bases for, and efficacy of, therapeutic countermeasures to the pernicious sequelae of compromised peripheral arterial function.
Scientific journal, English

Regulation of capillary hemodynamics by KATP channels in resting skeletal muscle.
Daniel M Hirai; Ayaka Tabuchi; Jesse C Craig; Trenton D Colburn; Timothy I Musch; David C Poole
Physiological reports, 9, 8, e14803, Apr. 2021, Peer-reviwed, True, ATP-sensitive K+ channels (KATP ) have been implicated in the regulation of resting vascular smooth muscle membrane potential and tone. However, whether KATP channels modulate skeletal muscle microvascular hemodynamics at the capillary level (the primary site for blood-myocyte O2 exchange) remains unknown. We tested the hypothesis that KATP channel inhibition would reduce the proportion of capillaries supporting continuous red blood cell (RBC) flow and impair RBC hemodynamics and distribution in perfused capillaries within resting skeletal muscle. RBC flux (fRBC ), velocity (VRBC ), and capillary tube hematocrit (Hctcap ) were assessed via intravital microscopy of the rat spinotrapezius muscle (n = 6) under control (CON) and glibenclamide (GLI; KATP channel antagonist; 10 µM) superfusion conditions. There were no differences in mean arterial pressure (CON:120 ± 5, GLI:124 ± 5 mmHg; p > 0.05) or heart rate (CON:322 ± 32, GLI:337 ± 33 beats/min; p > 0.05) between conditions. The %RBC-flowing capillaries were not altered between conditions (CON:87 ± 2, GLI:85 ± 1%; p > 0.05). In RBC-perfused capillaries, GLI reduced fRBC (CON:20.1 ± 1.8, GLI:14.6 ± 1.3 cells/s; p < 0.05) and VRBC (CON:240 ± 17, GLI:182 ± 17 µm/s; p < 0.05) but not Hctcap (CON:0.26 ± 0.01, GLI:0.26 ± 0.01; p > 0.05). The absence of GLI effects on the %RBC-flowing capillaries and Hctcap indicates preserved muscle O2 diffusing capacity (DO2 m). In contrast, GLI lowered both fRBC and VRBC thus impairing perfusive microvascular O2 transport (Q̇m) and lengthening RBC capillary transit times, respectively. Given the interdependence between diffusive and perfusive O2 conductances (i.e., %O2 extraction∝DO2 m/Q̇m), such GLI alterations are expected to elevate muscle %O2 extraction to sustain a given metabolic rate. These results support that KATP channels regulate capillary hemodynamics and, therefore, microvascular gas exchange in resting skeletal muscle.
Scientific journal, English

In vivo Ca2+ dynamics during cooling after eccentric contractions in rat skeletal muscle.
Ryo Takagi; Ayaka Tabuchi; Tomoyo Asamura; Seiya Hirayama; Ryo Ikegami; Yoshinori Tanaka; Daisuke Hoshino; David C Poole; Yutaka Kano
American journal of physiology. Regulatory, integrative and comparative physiology, 320, 2, R129-R137, 01 Feb. 2021, Peer-reviwed, True, The effect of cooling on in vivo intracellular calcium ion concentration [Ca2+]i after eccentric contractions (ECs) remains to be determined. We tested the hypothesis that cryotherapy following ECs promotes an increased [Ca2+]i and induces greater muscle damage in two muscles with substantial IIb and IIx fiber populations. The thin spinotrapezius (SPINO) muscles of Wistar rats were used for in vivo [Ca2+]i imaging, and tibialis anterior (TA) muscles provided greater fidelity and repeatability of contractile function measurements. SPINO [Ca2+]i was estimated using fura 2-AM and the magnitude, location, and temporal profile of [Ca2+]i determined as the temperature near the muscle surface post-ECs was decreased from 30°C (control) to 20°C or 10°C. Subsequently, in the TA, the effect of post-ECs cooling to 10°C on muscle contractile performance was determined at 1 and 2 days after ECs. TA muscle samples were examined by hematoxylin and eosin staining to assess damage. In SPINO, reducing the muscle temperature from 30°C to 10°C post-ECs resulted in a 3.7-fold increase in the spread of high [Ca2+]i sites generated by ECs (P < 0.05). These high [Ca2+]i sites demonstrated partial reversibility when rewarmed to 30°C. Dantrolene, a ryanodine receptor Ca2+ release inhibitor, reduced the presence of high [Ca2+] sites at 10°C. In the TA, cooling exacerbated ECs-induced muscle strength deficits via enhanced muscle fiber damage (P < 0.05). By demonstrating that cooling post-ECs potentiates [Ca2+]i derangements, this in vivo approach supports a putative mechanistic basis for how postexercise cryotherapy might augment muscle fiber damage and decrease subsequent exercise performance.
Scientific journal, English

Systemic NOS inhibition reduces contracting muscle oxygenation more in intact female than male rats.
Ayaka Tabuchi; Jesse C Craig; Daniel M Hirai; Trenton D Colburn; Yutaka Kano; David C Poole; Timothy I Musch
Lead, Nitric oxide : biology and chemistry, 100-101, 38-44, 01 Aug. 2020, Peer-reviwed, True, Females respond to baroreceptor stimulation with enhanced modulation of heart rate (HR) to regulate blood pressure and also express greater reliance on nitric oxide (NO) for vascular control compared to males. Sex differences in muscle oxygenation consequent to central hemodynamic challenge induced by systemic NO synthase (NOS) inhibition are unknown. We tested the hypotheses that systemic NOS inhibition would induce lower contracting skeletal muscle oxygenation in females compared to males. The spinotrapezius of Sprague-Dawley rats (females (♀) = 9, males (♂) = 9) was surgically exposed and contracted by electrical stimulation (180s, 1 Hz, ~6 V) under pentobarbital sodium anesthesia. Oxyphor G4 was injected into the muscle and phosphorescence quenching was used to measure the interstitial PO2 (PO2is, determined by O2 delivery-to-utilization matching) under control (Krebs-Henseleit solution) and after intra-arterial infusion of nitro-l-arginine methyl ester (l-NAME; NOS blockade; 10 mg kg-1). At rest, females showed a greater PO2is increase (ΔPO2is/ΔMAP) and HR (ΔHR/ΔMAP) reduction than males in response to the elevated MAP induced by systemic NOS inhibition (both p < 0.05). Following l-NAME, during the contracting steady-state, females exhibited lower PO2is than males (♂: 17.1 ± 1.4 vs ♀: 10.8 ± 1.4 mmHg, p < 0.05). The rate pressure product was lower in females than males (♂: 482 ± 14 vs ♀: 392 ± 29, p < 0.05) and correlated with the steady-state PO2is (r = 0.66, p < 0.05). These results support that females express greater reductions in HR than males in response to l-NAME-induced elevation of MAP via the baroreceptor reflex and provide new insights on how central hemodynamics affect skeletal muscle oxygenation in a sex-specific manner.
Scientific journal, English

Regional differences in Ca2+ entry along the proximal-middle-distal muscle axis during eccentric contractions in rat skeletal muscle.
Ayaka Tabuchi; Hiroaki Eshima; Yoshinori Tanaka; Shunsuke Nogami; Naoki Inoue; Mizuki Sudo; Hidetaka Okada; David C Poole; Yutaka Kano
Lead, Journal of applied physiology (Bethesda, Md. : 1985), 127, 3, 828-837, 01 Sep. 2019, Peer-reviwed, True, Eccentric (ECC) contraction-induced muscle damage is associated with calcium ion (Ca2+) influx from the extracellular milieu through stretch-activated channels. It remains unknown whether Ca2+ influx consequent to repetitive ECC contractions is nonuniform across different muscle regions. We tested the hypothesis that there are regional differences in Ca2+ entry along the proximal-middle-distal muscle axis. Tibialis anterior (TA) muscles of adult male Wistar rats were exposed by reflecting the overlying skin and fasciae and ECC contractions evoked by peroneal nerve stimulation paired with simultaneous ankle extension (50 times/set, 2 protocols: 1 set and 10 sets). During ECC in the proximal, middle, and distal TA, we determined 1) muscle fiber extension by high-speed camera (200 frames/s) and 2) Ca2+ accumulation by in vivo bioimaging (Ca2+-sensitive probe Fura-2-acetoxymethyl ester). Muscle fiber extension from resting was significantly different among regions (i.e., proximal, 4.0%: < middle, 11.2%: < distal, 17.0%; ECC phase length at 500th contraction). Intracellular Ca2+ accumulation after 1 set of ECC was higher in the distal (1.46 ± 0.04, P < 0.05) than the proximal (1.27 ± 0.04) or middle (1.26 ± 0.05) regions. However, this regional Ca2+ accumulation difference disappeared by 32.5 min after the 1 set protocol when the muscle was quiescent and by contraction set 5 for the 10-set protocol. The initial preferential ECC-induced Ca2+ accumulation observed distally was associated spatially with the greater muscle extension compared with that of the proximal and middle regions. Disappearance of the regional Ca2+ accumulation disparity in quiescent and ECC-contracting muscle might be explained, in part, by axial Ca2+ propagation and account for the uniformity of muscle damage across regions evident 3 days post-ECC.NEW & NOTEWORTHY After 1 set of 50 eccentric (ECC) contractions in the anterior tibialis muscle, intracellular Ca2+ ([Ca2+]i) accumulation evinces substantial regional heterogeneity that is spatially coherent with muscle length changes (i.e., distal [Ca2+]i > middle, proximal). However, irrespective of whether 50 or 500 ECC contractions are performed, this heterogeneity is subsequently abolished, at least in part, by axial intracellular Ca2+ propagation. This Ca2+ homogenization across regions is consistent with the absence of any interregional difference in muscle damage 3 days post-ECC.
Scientific journal, English

Central and peripheral factors mechanistically linked to exercise intolerance in heart failure with reduced ejection fraction.
Jesse C Craig; Trenton D Colburn; Jacob T Caldwell; Daniel M Hirai; Ayaka Tabuchi; Dryden R Baumfalk; Bradley J Behnke; Carl J Ade; Timothy I Musch; David C Poole
American journal of physiology. Heart and circulatory physiology, 317, 2, H434-H444, 01 Aug. 2019, Peer-reviwed, True, Exercise intolerance is a primary symptom of heart failure (HF); however, the specific contribution of central and peripheral factors to this intolerance is not well described. The hyperbolic relationship between exercise intensity and time to exhaustion (speed-duration relationship) defines exercise tolerance but is underused in HF. We tested the hypotheses that critical speed (CS) would be reduced in HF, resting central functional measurements would correlate with CS, and the greatest HF-induced peripheral dysfunction would occur in more oxidative muscle. Multiple treadmill-constant speed runs to exhaustion were used to quantify CS and D' (distance coverable above CS) in healthy control (Con) and HF rats. Central function was determined via left ventricular (LV) Doppler echocardiography [fractional shortening (FS)] and a micromanometer-tipped catheter [LV end-diastolic pressure (LVEDP)]. Peripheral O2 delivery-to-utilization matching was determined via phosphorescence quenching (interstitial Po2, Po2 is) in the soleus and white gastrocnemius during electrically induced twitch contractions (1 Hz, 8V). CS was lower in HF compared with Con (37 ± 1 vs. 44 ± 1 m/min, P < 0.001), but D' was not different (77 ± 8 vs. 69 ± 13 m, P = 0.6). HF reduced FS (23 ± 2 vs. 47 ± 2%, P < 0.001) and increased LVEDP (15 ± 1 vs. 7 ± 1 mmHg, P < 0.001). CS was related to FS (r = 0.72, P = 0.045) and LVEDP (r = -0.75, P = 0.02) only in HF. HF reduced soleus Po2 is at rest and during contractions (both P < 0.01) but had no effect on white gastrocnemius Po2 is (P > 0.05). We show in HF rats that decrements in central cardiac function relate directly with impaired exercise tolerance (i.e., CS) and that this compromised exercise tolerance is likely due to reduced perfusive and diffusive O2 delivery to oxidative muscles.NEW & NOTEWORTHY We show that critical speed (CS), which defines the upper boundary of sustainable activity, can be resolved in heart failure (HF) animals and is diminished compared with controls. Central cardiac function is strongly related with CS in the HF animals, but not controls. Skeletal muscle O2 delivery-to-utilization dysfunction is evident in the more oxidative, but not glycolytic, muscles of HF rats and is explained, in part, by reduced nitric oxide bioavailability.
Scientific journal, English

In vivo環境下におけるマウス骨格筋ミトコンドリア内Ca²⁺動態の可視化—In vivo visualization of mitochondrial Ca²⁺ dynamics in mouse skeletal muscle during contractions
田中 嘉法; 田渕 絢香; 白川 英樹; 狩野 豊
東京 : 北隆館, Jan. 2024, アグリバイオ = Agricultural biotechnology, 8, 1, 60-64, Japanese, 2432-5511, AA12770259

In vivo環境下におけるマウス骨格筋ミトコンドリア内Ca²⁺動態の可視化—In vivo visualization of mitochondrial Ca²⁺ dynamics in mouse skeletal muscle during contractions
田中 嘉法; 田渕 絢香; 白川 英樹; 狩野 豊
東京 : ニューサイエンス社, Apr. 2023, 細胞, 55, 5, 335-338, Japanese, 1346-7557, AA11382662

ラット骨格筋の温度低下が細胞内カルシウムイオン濃度に及ぼす影響
高木 領; 池上 諒; 田渕 絢香; 田中 嘉法; 狩野 豊
公益社団法人 日本理学療法士協会, 2020, 理学療法学Supplement, 47S1, B-160_2-B-160_2, Japanese, 130008010737

SERCA mediated thermogenesis during contraction-relaxation cycle in rat skeletal muscle in vivo
Ayaka Tabuchi; Yoshinori Tanaka; David C Poole; Yutaka Kano
Poster presentation, American Physiological Summit 2024, Peer-reviewed
05 Apr. 2024
04 Apr. 2024- 07 Apr. 2024

Quantitative Evaluation of Waveguide Digital Holographic Microscopy for Bioimaging
田渕絢香; 林健太; Maryam Faheem; 渡邉恵理子
Optics & Photonics Japan 2023
28 Nov. 2023

The effect of Cmah inactivation on transcapillary PO2 dynamics and gradients in mice skeletal muscle during contraction
Ayaka Tabuchi; Takuto Inoue; David C Poole; Yutaka Kano
The International Society on Oxygen Transport to Tissue 2023
28 Sep. 2023
27 Sep. 2023- 01 Oct. 2023

High-speed 3D color Planar Lightwave Circuit Digital Holographic Microscope towards the observation of mammalian cells
Ayaka Tabuchi; Kenta Hayashi; Maryam Faheem; Yutaka Kano; Eriko Watanabe
The 9th Biomedical Imaging and Sensing Confrerences, Peer-reviewed
20 Apr. 2023

Upregulation of mitochondrial calcium regulation proteins following the eccentric contraction in rat skeletal muscle
Ayaka Tabuchi; Ryo Takagi; Yudai Kikuchi; Yutaka Kano
Poster presentation, 第100回日本生理学会, Peer-reviewed
15 Mar. 2023

発育期の骨格筋細胞の成⻑にともなう 細胞内カルシウムイオン動態の変化
田渕 絢香; 髙木 領; 狩野 豊
Oral presentation, 第9回骨格筋生物学研究会
05 Mar. 2023

In vivoバイオイメージングによる骨格筋適応を制御するカルシウムイオンパターンの解明
田渕 絢香
Nominated symposium, 第28回医用近赤外線分光法研究会・第26回酸素ダイナミクス研究会, Invited
01 Oct. 2022

Pharmacological Inhibition Of Ryanodine Receptors Immediately After Eccentric Contractions Exercise Effectively Reduces Exercise-induced Muscle Damage In Rat Skeletal Muscle
Ayaka Tabuchi; Yoshinori Tanaka; Ryo Takagi; David Poole; Yutaka Kano
English, American College Sports and Medicine Annual Meeting 2022, LIPPINCOTT WILLIAMS & WILKINS, Peer-reviewed
Sep. 2022
Sep. 2022 Sep. 2022

伸張性収縮の繰り返し負荷は細胞内カルシウムイオン蓄積を抑制する
田渕 絢香; 菊池 雄大; 髙木 領; 狩野 豊
第77回日本体力医学会, Peer-reviewed
Sep. 2022

骨格筋の変化をもたらす細胞内カルシウムイオン変化
田渕 絢香
第二回基礎理工学研究会, Invited
Dec. 2021

伸張性収縮後の筋細胞内カルシウムイオン時空間変化と筋損傷との関係
田渕 絢香; 田中 嘉法; 高木 領; 白川 英樹; 狩野 豊
第76回日本体力医学会, Peer-reviewed
Sep. 2021

運動誘発性の損傷骨格筋に特徴的な細胞内カルシウムイオン変動パターン
田渕 絢香; 田中 嘉法; 高木 領; 白川 英樹; 狩野 豊
第75回日本体力医学会, Peer-reviewed
Sep. 2020

Skeletal Muscle Capillary Hemodynamics in Rats with Heart Failure with Preserved Ejection Fraction
Daniel Hirai; Ayaka Tabuchi; Jesse Craig; Trenton Colburn; Jacob Caldwell; Carl Ade; Dryden Baumfalk; Alex Opoku-Acheampong; Brad Behnke; K. Hageman; Timothy Musch; David Poole
English, Experimental Biology 2020, WILEY, Peer-reviewed, 0
Apr. 2020
Apr. 2020 Apr. 2020

伸張性収縮に伴う筋部位別の伸展量および細胞内カルシウムイオンの蓄積動態
田渕 絢香; 江島 弘晃; 田中 嘉法; 須藤 みず紀; 岡田 英孝; 狩野 豊
第74回日本体力医学会, Peer-reviewed
Sep. 2019

損傷再生過程における細胞内カルシウムイオンダイナミクスとmTOR系のリン酸化
田渕 絢香; 白川 英樹; 芝口 翼; 杉浦 崇夫; 狩野 豊
第73回日本体力医学会, Peer-reviewed
Sep. 2018

Dynamics of Skeletal Muscle Interstitial PO 2 During Recovery from Contractions
Daniel M. Hirai; Trenton D. Colburn; Jesse C. Craig; Ayaka Tabuchi; Timothy I. Musch; David C. Poole
English, American College Sports and Medicine, LIPPINCOTT WILLIAMS & WILKINS, Peer-reviewed
May 2018
May 2018 May 2018

Critical Speed in Heart Failure Rats: The Central Determinant of Performance
Jesse C. Craig; Joseph H. Merino; Daniel M. Hirai; Trenton D. Colburn; Ayaka Tabuchi; Jacob T. Caldwell; Carl J. Ade; Timothy I. Musch; David C. Poole
English, American College Sports and Medicine, LIPPINCOTT WILLIAMS & WILKINS, Peer-reviewed
May 2018
May 2018 May 2018

Regulation of Capillary Hemodynamics by K-ATP Channels in Resting Skeletal Muscle
Daniel M. Hirai; Jesse C. Craig; Trenton D. Colburn; Ayaka Tabuchi; K. Sue Hageman; Timothy I. Musch; David C. Poole
English, Experimental Biology 2018, FEDERATION AMER SOC EXP BIOL, Peer-reviewed, 0
Apr. 2018
Apr. 2018 Apr. 2018

Central Cardiac Determinants of the Speed-duration Relationship in Heart Failure Rats
Jesse C. Craig; Trenton D. Colburn; Jacob T. Caldwell; Daniel M. Hirai; Ayaka Tabuchi; Joseph H. Merino; Carl J. Ade; David C. Poole; Timothy I. Musch
English, Experimental Biology 2018, FEDERATION AMER SOC EXP BIOL, Peer-reviewed, 0
Apr. 2018
Apr. 2018 Apr. 2018

Interstitial PO2 Dynamics During Contractions in Healthy Skeletal Muscle: Relationship to Oxidative Capacity and Nitric Oxide Bioavailability
Trenton D. Colburn; Jesse C. Craig; Daniel M. Hirai; Ayaka Tabuchi; K. Sue Hageman; Timothy I. Musch; David C. Poole
English, Experimental Biology 2018, FEDERATION AMER SOC EXP BIOL, Peer-reviewed, 0
Apr. 2018
Apr. 2018 Apr. 2018

In Vivo Intracellular Ca2+Dynamics Over 7 Days Following Eccentric Contractions In Rat Skeletal Muscle
Ayaka Tabuchi; Hideki Shirakawa; David C. Poole; Yutaka Kano
English, American College Sports and Medicine, LIPPINCOTT WILLIAMS & WILKINS, Peer-reviewed
May 2017
May 2017 May 2017

伸張性収縮後に観察される筋細胞内カルシウムイオンダイナミクス
田渕 絢香; 狩野 豊
第71回日本体力医学会, Peer-reviewed
Sep. 2016

2018 - Present
American Physiological Society

May 2017 - Present
American College of Sports Medicine

2014 - Present
日本体力医学会

生体ハイパースペクトルイメージングによる骨格筋の質の新たな評価法創出
田渕 絢香
日本学術振興会, 科学研究費助成事業, 電気通信大学, 若手研究, 24K20597
01 Apr. 2024 - 31 Mar. 2027

運動による筋損傷を局所限定的にする細胞内ダイナミクスの解明
田渕 絢香
日本学術振興会, 科学研究費助成事業, 電気通信大学, 研究活動スタート支援, 23K19921
31 Aug. 2023 - 31 Mar. 2025

骨格筋の運命を決定するカルシウムイオン時空間パターンと細胞内機構の解明
田渕 絢香
日本学術振興会, 科学研究費助成事業 特別研究員奨励費, 電気通信大学, 特別研究員奨励費, 本研究は，骨格筋細胞の損傷，再生，肥大といった適応を誘導するそれぞれに特異的な細胞内カルシウムイオン時空間パターンが存在するという仮説を検証することを目的としている． まず，伸張性収縮による筋損傷過程に着目しin vivoバイオイメージング技法細胞内カルシウム動態の観察を行った．その結果，伸張性収縮中のカルシウムイオン蓄積に引き続き，5時間後においてもカルシウムイオン濃度が高く，さらに部位局所的に蓄積していることが明らかになった．これは，筋損傷の形態的特徴が顕著となる24時間後に先行して生じていた．このカルシウムイオンパターンを形成している要素としてリアノジン受容体に着目したところ，リアノジン受容体を阻害すると5時間後におけるカルシウムイオンの蓄積および24時間後の筋損傷が抑制されることが示された．一方で，伸張性収縮中のカルシウムイオン流入経路である伸展活性化チャネルの阻害は，5時間後におけるカルシウムイオン動態に影響を与えなかった．以上の結果から，伸張性収縮中の伸展活性化チャネルを介したカルシウムイオン流入に引き続き，収縮後もリアノジン受容体からのカルシウムイオン漏出によるカルシウムイオン蓄積パターンが存在し，筋の損傷をもたらしていることが示された．この結果は，2021年9月で行われた体力医学会で発表を行い，2022年1月に国際学術誌へ掲載された． また，筋が著しい肥大を遂げる発育過程におけるカルシウムイオン動態の観察に試みた．身体の大きさも異なる3，6，12週齢のラットを対象に in vivoバイオイメージング技法によるカルシウムイオン動態観察技法を確立した．さらに生化学的手法から，週齢によって異なるカルシウムイオンハンドリング機構を形成している可能性を示す結果が得られた．, 21J14283
28 Apr. 2021 - 31 Mar. 2023

女性特有の運動パフォーマンスの変化はなぜ生じるのか：性周期と筋細胞内環境の関係性からの探究
（財）ヤマハ発動機スポーツ振興財団, スポーツチャレンジ研究助成, Principal investigator
Apr. 2022 - Mar. 2023

骨格筋の適応を決定する細胞内カルシウムイオンの変動パターンの解明
日本科学協会, 笹川科学研究助成, Principal investigator
Apr. 2020 - Mar. 2021