Synaptic currents represent a major contribution to the local field potential (LFP) in brain tissue, but the respective contribution of excitatory and inhibitory synapses is not known. Here, we provide estimates of this contribution by using computational models of hippocampal pyramidal neurons, constrained by in vitro recordings. We focus on the unitary LFP (uLFP) generated by single neurons in the CA3 region of the hippocampus. We first reproduce experimental results for hippocampal basket cells, and in particular how inhibitory uLFP are distributed within hippocampal layers. Next, we calculate the uLFP generated by pyramidal neurons, using morphologically-reconstructed CA3 pyramidal cells. The model shows that the excitatory uLFP is of small amplitude, smaller than inhibitory uLFPs. Indeed, when the two are simulated together, inhibitory uLFPs mask excitatory uLFPs, which might create the illusion that the inhibitory field is generated by pyramidal cells. These results provide an explanation for the observation that excitatory and inhibitory uLFPs are of the same polarity, in vivo and in vitro. These results also show that somatic inhibitory currents are large contributors of the LFP, which is important information to interpret this signal. Finally, the results of our model might form the basis of a simple method to compute the LFP, which could be applied to point neurons for each cell type, thus providing a simple biologically-grounded method to calculate LFPs from neural networks.
{"title":"Modelling unitary fields and the single‐neuron contribution to local field potentials in the hippocampus","authors":"Maria Teleńczuk, B. Teleńczuk, A. Destexhe","doi":"10.1101/602953","DOIUrl":"https://doi.org/10.1101/602953","url":null,"abstract":"Synaptic currents represent a major contribution to the local field potential (LFP) in brain tissue, but the respective contribution of excitatory and inhibitory synapses is not known. Here, we provide estimates of this contribution by using computational models of hippocampal pyramidal neurons, constrained by in vitro recordings. We focus on the unitary LFP (uLFP) generated by single neurons in the CA3 region of the hippocampus. We first reproduce experimental results for hippocampal basket cells, and in particular how inhibitory uLFP are distributed within hippocampal layers. Next, we calculate the uLFP generated by pyramidal neurons, using morphologically-reconstructed CA3 pyramidal cells. The model shows that the excitatory uLFP is of small amplitude, smaller than inhibitory uLFPs. Indeed, when the two are simulated together, inhibitory uLFPs mask excitatory uLFPs, which might create the illusion that the inhibitory field is generated by pyramidal cells. These results provide an explanation for the observation that excitatory and inhibitory uLFPs are of the same polarity, in vivo and in vitro. These results also show that somatic inhibitory currents are large contributors of the LFP, which is important information to interpret this signal. Finally, the results of our model might form the basis of a simple method to compute the LFP, which could be applied to point neurons for each cell type, thus providing a simple biologically-grounded method to calculate LFPs from neural networks.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"21 1","pages":"3957 - 3972"},"PeriodicalIF":0.0,"publicationDate":"2019-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84986642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-11-17DOI: 10.1113/jphysiol.1892.sp000438
H. Wood
{"title":"The Effects of Drugs and other Agencies upon the Respiratory Movements","authors":"H. Wood","doi":"10.1113/jphysiol.1892.sp000438","DOIUrl":"https://doi.org/10.1113/jphysiol.1892.sp000438","url":null,"abstract":"","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"64 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88141603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Placental insufficiency and intrauterine growth restriction (IUGR) of the fetus affects approximately 8% of all pregnancies and is associated with short‐ and long‐term disturbances in metabolism. In pregnant sheep, experimental models with a small, defective placenta that restricts delivery of nutrients and oxygen to the fetus result in IUGR. Low blood oxygen concentrations increase fetal plasma catecholamine concentrations, which lower fetal insulin concentrations. All of these observations in sheep models with placental insufficiency are consistent with cases of human IUGR. We propose that sustained high catecholamine concentrations observed in the IUGR fetus produce developmental adaptations in pancreatic β‐cells that impair fetal insulin secretion. Experimental evidence supporting this hypothesis shows that chronic elevation in circulating catecholamines in IUGR fetuses persistently inhibits insulin concentrations and secretion. Elevated catecholamines also allow for maintenance of a normal fetal basal metabolic rate despite low fetal insulin and glucose concentrations while suppressing fetal growth. Importantly, a compensatory augmentation in insulin secretion occurs following inhibition or cessation of catecholamine signalling in IUGR fetuses. This finding has been replicated in normally grown sheep fetuses following a 7‐day noradrenaline (norepinephrine) infusion. Together, these programmed effects will potentially create an imbalance between insulin secretion and insulin‐stimulated glucose utilization in the neonate which probably explains the transient hyperinsulinism and hypoglycaemia in some IUGR infants.
{"title":"Fetal adaptations in insulin secretion result from high catecholamines during placental insufficiency","authors":"S. Limesand, P. Rozance","doi":"10.1113/JP273324","DOIUrl":"https://doi.org/10.1113/JP273324","url":null,"abstract":"Placental insufficiency and intrauterine growth restriction (IUGR) of the fetus affects approximately 8% of all pregnancies and is associated with short‐ and long‐term disturbances in metabolism. In pregnant sheep, experimental models with a small, defective placenta that restricts delivery of nutrients and oxygen to the fetus result in IUGR. Low blood oxygen concentrations increase fetal plasma catecholamine concentrations, which lower fetal insulin concentrations. All of these observations in sheep models with placental insufficiency are consistent with cases of human IUGR. We propose that sustained high catecholamine concentrations observed in the IUGR fetus produce developmental adaptations in pancreatic β‐cells that impair fetal insulin secretion. Experimental evidence supporting this hypothesis shows that chronic elevation in circulating catecholamines in IUGR fetuses persistently inhibits insulin concentrations and secretion. Elevated catecholamines also allow for maintenance of a normal fetal basal metabolic rate despite low fetal insulin and glucose concentrations while suppressing fetal growth. Importantly, a compensatory augmentation in insulin secretion occurs following inhibition or cessation of catecholamine signalling in IUGR fetuses. This finding has been replicated in normally grown sheep fetuses following a 7‐day noradrenaline (norepinephrine) infusion. Together, these programmed effects will potentially create an imbalance between insulin secretion and insulin‐stimulated glucose utilization in the neonate which probably explains the transient hyperinsulinism and hypoglycaemia in some IUGR infants.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"148 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77787454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Cottrell, T. Tropea, L. Ormesher, S. Greenwood, M. Wareing, E. Johnstone, J. Myers, C. Sibley
Fetal growth restriction (FGR) affects around 5% of pregnancies and is associated with significant short‐ and long‐term adverse outcomes. A number of factors can increase the risk of FGR, one of which is poor maternal diet. In terms of pathology, both clinically and in many experimental models of FGR, impaired uteroplacental vascular function is implicated, leading to a reduction in the delivery of oxygen and nutrients to the developing fetus. Whilst mechanisms underpinning impaired uteroplacental vascular function are not fully understood, interventions aimed at enhancing nitric oxide (NO) bioavailability remain a key area of interest in obstetric research. In addition to endogenous NO production from the amino acid l‐arginine, via nitric oxide synthase (NOS) enzymes, research in recent years has established that significant NO can be derived from dietary nitrate, via the ‘alternative NO pathway’. Dietary nitrate, abundant in green leafy vegetables and beetroot, can increase NO bioactivity, conferring beneficial effects on cardiovascular function and blood flow. Given the beneficial effects of dietary nitrate supplementation to date in non‐pregnant humans and animals, current investigations aim to assess the therapeutic potential of this approach in pregnancy to enhance NO bioactivity, improve uteroplacental vascular function and increase fetal growth.
{"title":"Dietary interventions for fetal growth restriction – therapeutic potential of dietary nitrate supplementation in pregnancy","authors":"E. Cottrell, T. Tropea, L. Ormesher, S. Greenwood, M. Wareing, E. Johnstone, J. Myers, C. Sibley","doi":"10.1113/JP273331","DOIUrl":"https://doi.org/10.1113/JP273331","url":null,"abstract":"Fetal growth restriction (FGR) affects around 5% of pregnancies and is associated with significant short‐ and long‐term adverse outcomes. A number of factors can increase the risk of FGR, one of which is poor maternal diet. In terms of pathology, both clinically and in many experimental models of FGR, impaired uteroplacental vascular function is implicated, leading to a reduction in the delivery of oxygen and nutrients to the developing fetus. Whilst mechanisms underpinning impaired uteroplacental vascular function are not fully understood, interventions aimed at enhancing nitric oxide (NO) bioavailability remain a key area of interest in obstetric research. In addition to endogenous NO production from the amino acid l‐arginine, via nitric oxide synthase (NOS) enzymes, research in recent years has established that significant NO can be derived from dietary nitrate, via the ‘alternative NO pathway’. Dietary nitrate, abundant in green leafy vegetables and beetroot, can increase NO bioactivity, conferring beneficial effects on cardiovascular function and blood flow. Given the beneficial effects of dietary nitrate supplementation to date in non‐pregnant humans and animals, current investigations aim to assess the therapeutic potential of this approach in pregnancy to enhance NO bioactivity, improve uteroplacental vascular function and increase fetal growth.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74157282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R. C. Wüst, M. Helmes, Jody L. Martin, Thomas J. T. Van der Wardt, R. Musters, J. van der Velden, G. Stienen
Calcium ions regulate mitochondrial ATP production and contractile activity and thus play a pivotal role in matching energy supply and demand in cardiac muscle. The magnitude and kinetics of the changes in free mitochondrial calcium concentration in cardiac myocytes are largely unknown. Rapid stimulation frequency‐dependent increases but relatively slow decreases in free mitochondrial calcium concentration were observed in rat cardiac myocytes. This asymmetry caused a rise in the mitochondrial calcium concentration with stimulation frequency. These results provide insight into the mechanisms of mitochondrial calcium uptake and release that are important in healthy and diseased myocardium.
{"title":"Rapid frequency‐dependent changes in free mitochondrial calcium concentration in rat cardiac myocytes","authors":"R. C. Wüst, M. Helmes, Jody L. Martin, Thomas J. T. Van der Wardt, R. Musters, J. van der Velden, G. Stienen","doi":"10.1113/JP273589","DOIUrl":"https://doi.org/10.1113/JP273589","url":null,"abstract":"Calcium ions regulate mitochondrial ATP production and contractile activity and thus play a pivotal role in matching energy supply and demand in cardiac muscle. The magnitude and kinetics of the changes in free mitochondrial calcium concentration in cardiac myocytes are largely unknown. Rapid stimulation frequency‐dependent increases but relatively slow decreases in free mitochondrial calcium concentration were observed in rat cardiac myocytes. This asymmetry caused a rise in the mitochondrial calcium concentration with stimulation frequency. These results provide insight into the mechanisms of mitochondrial calcium uptake and release that are important in healthy and diseased myocardium.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79305905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hypercapnia or parafacial respiratory group (pFRG) disinhibition at normocapnia evokes active expiration in rats by recruitment of pFRG late‐expiratory (late‐E) neurons. We show that hypercapnia simultaneously evoked active expiration and exaggerated glottal dilatation by late‐E synaptic excitation of abdominal, hypoglossal and laryngeal motoneurons. Simultaneous rhythmic expiratory activity in previously silent pFRG late‐E neurons, which did not express the marker of ventral medullary CO2‐sensitive neurons (transcription factor Phox2b), was also evoked by hypercapnia. Hypercapnia‐evoked active expiration, neural and neuronal late‐E activities were eliminated by pFRG inhibition, but not after blockade of synaptic excitation. Hypercapnia produces disinhibition of non‐chemosensitive pFRG late‐E neurons to evoke active expiration and concomitant cranial motor respiratory responses controlling the oropharyngeal and upper airway patency.
{"title":"Non‐chemosensitive parafacial neurons simultaneously regulate active expiration and airway patency under hypercapnia in rats","authors":"Alan A de Britto, D. Moraes","doi":"10.1113/JP273335","DOIUrl":"https://doi.org/10.1113/JP273335","url":null,"abstract":"Hypercapnia or parafacial respiratory group (pFRG) disinhibition at normocapnia evokes active expiration in rats by recruitment of pFRG late‐expiratory (late‐E) neurons. We show that hypercapnia simultaneously evoked active expiration and exaggerated glottal dilatation by late‐E synaptic excitation of abdominal, hypoglossal and laryngeal motoneurons. Simultaneous rhythmic expiratory activity in previously silent pFRG late‐E neurons, which did not express the marker of ventral medullary CO2‐sensitive neurons (transcription factor Phox2b), was also evoked by hypercapnia. Hypercapnia‐evoked active expiration, neural and neuronal late‐E activities were eliminated by pFRG inhibition, but not after blockade of synaptic excitation. Hypercapnia produces disinhibition of non‐chemosensitive pFRG late‐E neurons to evoke active expiration and concomitant cranial motor respiratory responses controlling the oropharyngeal and upper airway patency.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90880518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The dynamic metabolic range of skeletal muscle necessitates an equally dynamic blood flow requirement, to the point where the demand for skeletal muscle blood flow during intense bouts of large muscle mass exercise can theoretically ‘outstrip’ the heart's ability to generate the cardiac output necessary for maintaining sufficient mean arterial pressure (MAP) and muscle perfusion. This article is protected by copyright. All rights reserved
{"title":"Characterizing the sympatholytic role of endothelial‐dependent vasodilator signalling during handgrip exercise","authors":"Iain R Lamb, N. Novielli","doi":"10.1113/JP273806","DOIUrl":"https://doi.org/10.1113/JP273806","url":null,"abstract":"The dynamic metabolic range of skeletal muscle necessitates an equally dynamic blood flow requirement, to the point where the demand for skeletal muscle blood flow during intense bouts of large muscle mass exercise can theoretically ‘outstrip’ the heart's ability to generate the cardiac output necessary for maintaining sufficient mean arterial pressure (MAP) and muscle perfusion. \u0000 \u0000This article is protected by copyright. All rights reserved","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"42 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85312811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Bartlett, Julia D. Miehm, Liam F. Fitzgerald, C. Straight
Endurance training improves skeletal muscle oxidative capacity, but the molecular adaptations that drive this process are not fully understood. Specifically, whether oxidative capacity is improved solely by augmentations in mitochondrial quantity, or by enhanced mitochondrial quality as well, is unclear. For example, compared to active individuals, elite endurance athletes exhibit superior in vitro oxidative capacity even when normalised to citrate synthase (CS) activity, a common marker of mitochondrial quantity (Jacobs & Lundby, 2013). Two important questions emerge from these results: (1) what molecular or enzymatic aspects of mitochondrial composition might allow rates of in vitro oxidative capacity to increase for a given mitochondrial volume, and (2) what endurance training methods are best suited to stimulate these positive adaptations? Adaptations to endurance training have traditionally been studied following a period of moderate intensity continuous training (MICT), which is characterised by prolonged periods of aerobic activity at submaximal workloads (i.e. high volume training). More recently, interest has shifted towards high intensity interval training (HIIT), which involves repeated bouts of vigorous-intensity exercise interspersed with periods of recovery. Daussin et al. (2008) reported that in vitro oxidative capacity is significantly improved by HIIT, but not by MICT. Larsen et al. (2013) demonstrated that as few as six sessions of HIIT are sufficient to improve in vivo markers of skeletal muscle oxidative capacity, measured as the maximal rate of phosphocreatine resynthesis. However, these studies did not “normalise” oxidative capacity measurements to mitochondrial quantity, nor did they measure changes in mitochondrial enzymatic composition, making it difficult to infer the molecular mechanisms that control measures of oxidative capacity and how training intensity may influence these changes. In an article in The Journal of Physiology, MacInnis et al. (2016) attempted to address this gap in the literature by comparing changes in whole muscle and mitochondria-specific in vitro oxidative capacity after 2 weeks of MICT and HIIT. To compare the different training modalities, they used single-leg cycle ergometry, which allowed all participants (n=10 young males) to perform both MICT and HIIT over the same training period and serve as their own controls. Peak aerobic capacity (Wpeak) was measured on each leg using a ramp protocol before and after 2 weeks of endurance training. Participants completed six sessions of single-leg MICT (30 min at 50% Wpeak) and HIIT (4 bouts of 5 min at 65% Wpeak and 2.5 min at 20% Wpeak). Muscle biopsies were taken from the vastus lateralis of each leg preand post-training to measure markers of mitochondrial composition and mitochondrial oxidative capacity. Markers of mitochondrial composition included CS (used as a marker for mitochondrial quantity), cytochrome c oxidase subunit 4 (COXIV), NADH:ubiquin
耐力训练可以提高骨骼肌的氧化能力，但驱动这一过程的分子适应机制尚不完全清楚。具体来说，氧化能力的提高是仅仅通过线粒体数量的增加，还是通过线粒体质量的提高，目前还不清楚。例如，与活跃的个体相比，优秀的耐力运动员即使在柠檬酸合酶(CS)活性正常化时也表现出卓越的体外氧化能力(CS是线粒体数量的常见标志)(Jacobs & Lundby, 2013)。从这些结果中出现了两个重要的问题:(1)线粒体组成的哪些分子或酶方面可能允许体外氧化能力的速率在给定的线粒体体积下增加，(2)什么样的耐力训练方法最适合刺激这些积极的适应?对耐力训练的适应性传统上是在一段时间的中等强度连续训练(MICT)后进行研究的，其特征是在次最大负荷下进行长时间的有氧运动(即大容量训练)。最近，人们的兴趣转向了高强度间歇训练(HIIT)，它包括在恢复期中反复进行高强度运动。Daussin等人(2008)报道HIIT可显著提高体外氧化能力，而MICT不能。Larsen等人(2013)证明，只需6次HIIT就足以提高骨骼肌氧化能力的体内标志物，以磷酸肌酸再合成的最大速率来衡量。然而，这些研究并没有使线粒体数量的氧化能力测量“正常化”，也没有测量线粒体酶组成的变化，因此很难推断控制氧化能力测量的分子机制以及训练强度如何影响这些变化。在《生理学杂志》(The Journal of Physiology)的一篇文章中，MacInnis等人(2016)试图通过比较MICT和HIIT两周后全肌肉和线粒体特异性体外氧化能力的变化来解决这一文献空白。为了比较不同的训练方式，他们使用单腿循环几何法，允许所有参与者(n=10名年轻男性)在相同的训练期间同时进行MICT和HIIT，并作为他们自己的对照。在2周耐力训练之前和之后，使用坡道方案测量每条腿的峰值有氧能力(Wpeak)。参与者完成了6次单腿MICT(50%峰值时30分钟)和HIIT(4次，65%峰值时5分钟，20%峰值时2.5分钟)。训练前后分别对每条腿的股外侧肌进行肌肉活检，测量线粒体组成和线粒体氧化能力的标志物。线粒体组成标记包括CS(作为线粒体数量的标记)、细胞色素c氧化酶亚基4 (COXIV)、NADH:泛醌氧化还原酶亚基A9 (NDUFA9)和丝裂酶2 (MFN2);后三者在肌球蛋白重链(MHC) I和IIA纤维中测定蛋白质含量。采用底物解偶联剂抑制剂滴定法，在体外测量渗透肌纤维的氧化能力，通过电子传递链的配合物I和II，可以分别测定最大的O2呼吸速率(jo2)。质量特异性jo2计算为jo2 /肌肉活检质量，而线粒体特异性jo2计算为质量特异性jo2归一化至CS含量。与MICT相比，HIIT后全肌CS活动的增加明显更大(分别为+39%和+11%)。HIIT还通过复合体I (HIIT +22% vs. MICT -7%)和复合体I+II (HIIT +22% vs. MICT -9%)显著改善了质量特异性jo2。相比之下，两种训练方法都没有促进线粒体特异性jo2的改善。尽管MICT和HIIT都刺激了COXIV、NDUFA9和MFN2蛋白含量的增加，但这些增加似乎都不是纤维类型特异性的。与作者的假设一致，HIIT在改善骨骼肌线粒体数量(即CS活性)方面比MICT更有效，这与质量特异性jo2的更大增加相吻合。然而，这两种训练方法都没有显著改善线粒体特异性的jo2(即线粒体质量)。基于这些观察，耐力训练可能先于线粒体质量刺激线粒体丰度的变化。换句话说，也许线粒体质量的改善只有在线粒体丰度增加到肌纤维空间限制所允许的极限时才会发生。在几周的时间内逐渐跟踪这些变化，看看质量和线粒体特异性jo2的变化是否与时间有关，这将是一件有趣的事情。 我们还感兴趣的是，训练方法对MHC I和IIA肌肉纤维中COXIV、NDUFA9和MFA2蛋白含量的变化没有差异。虽然先前的研究表明，6次HIIT足以提高骨骼肌的氧化能力(Daussin etal . 2008;Larsen et al. 2013)，这些研究中的间歇运动强度通常远高于MacInnis et al.(2016)所采用的Wpeak的65%。因此，HIIT和MICT规定的相对适度的训练强度差异(分别为65% vs 50% Wpeak)可能不足以在两种训练方法之间引起不同的能量过载。也许增加HIIT方案的强度(例如80%峰值)和缩短间歇时间会在两种训练方案之间引起不同的反应。也有可能是电子传递链以外的酶限制了jo2和氧化能力。例如，在体外呼吸测量中，线粒体jo2经常受到大剂量饱和ADP的刺激。在这些条件下，最大jo2基本上受到ADP转运速率的限制
{"title":"Do changes in mitochondrial quality contribute to increases in skeletal muscle oxidative capacity following endurance training?","authors":"M. Bartlett, Julia D. Miehm, Liam F. Fitzgerald, C. Straight","doi":"10.1113/JP273809","DOIUrl":"https://doi.org/10.1113/JP273809","url":null,"abstract":"Endurance training improves skeletal muscle oxidative capacity, but the molecular adaptations that drive this process are not fully understood. Specifically, whether oxidative capacity is improved solely by augmentations in mitochondrial quantity, or by enhanced mitochondrial quality as well, is unclear. For example, compared to active individuals, elite endurance athletes exhibit superior in vitro oxidative capacity even when normalised to citrate synthase (CS) activity, a common marker of mitochondrial quantity (Jacobs & Lundby, 2013). Two important questions emerge from these results: (1) what molecular or enzymatic aspects of mitochondrial composition might allow rates of in vitro oxidative capacity to increase for a given mitochondrial volume, and (2) what endurance training methods are best suited to stimulate these positive adaptations? Adaptations to endurance training have traditionally been studied following a period of moderate intensity continuous training (MICT), which is characterised by prolonged periods of aerobic activity at submaximal workloads (i.e. high volume training). More recently, interest has shifted towards high intensity interval training (HIIT), which involves repeated bouts of vigorous-intensity exercise interspersed with periods of recovery. Daussin et al. (2008) reported that in vitro oxidative capacity is significantly improved by HIIT, but not by MICT. Larsen et al. (2013) demonstrated that as few as six sessions of HIIT are sufficient to improve in vivo markers of skeletal muscle oxidative capacity, measured as the maximal rate of phosphocreatine resynthesis. However, these studies did not “normalise” oxidative capacity measurements to mitochondrial quantity, nor did they measure changes in mitochondrial enzymatic composition, making it difficult to infer the molecular mechanisms that control measures of oxidative capacity and how training intensity may influence these changes. In an article in The Journal of Physiology, MacInnis et al. (2016) attempted to address this gap in the literature by comparing changes in whole muscle and mitochondria-specific in vitro oxidative capacity after 2 weeks of MICT and HIIT. To compare the different training modalities, they used single-leg cycle ergometry, which allowed all participants (n=10 young males) to perform both MICT and HIIT over the same training period and serve as their own controls. Peak aerobic capacity (Wpeak) was measured on each leg using a ramp protocol before and after 2 weeks of endurance training. Participants completed six sessions of single-leg MICT (30 min at 50% Wpeak) and HIIT (4 bouts of 5 min at 65% Wpeak and 2.5 min at 20% Wpeak). Muscle biopsies were taken from the vastus lateralis of each leg preand post-training to measure markers of mitochondrial composition and mitochondrial oxidative capacity. Markers of mitochondrial composition included CS (used as a marker for mitochondrial quantity), cytochrome c oxidase subunit 4 (COXIV), NADH:ubiquin","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86062537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ángela López-Gil, Carmen Nanclares, I. Méndez-López, Carmen Martínez-Ramírez, C. de los Ríos, J. F. Padín-Nogueira, M. Montero, L. Gandía, Antonio G. García
Upon repeated application of short ACh pulses to C57BL6J mouse chromaffin cells, the amperometrically monitored secretory responses promptly decayed to a steady‐state level of around 25% of the initial response. A subsequent K+ pulse, however, overcame such decay. These data suggest that mouse chromaffin cells have a ready release‐vesicle pool that is selectively recruited by the physiological neurotransmitter ACh. The ACh‐sensitive vesicle pool is refilled and maintained by the rate of Ca2+ delivery from mitochondria to the cytosol, through the mitochondrial Na+/Ca2+ exchanger (mNCX). ITH12662, a novel blocker of the mNCX, prevented the decay of secretion elicited by ACh pulses and delayed the rate of [Ca2+]c clearance. This regulatory pathway may be physiologically relevant in situations of prolonged stressful conflicts where a sustained catecholamine release is regulated by mitochondrial Ca2+ circulation through the mNCX, which couples respiration and ATP synthesis to long‐term stimulation of chromaffin cells by endogenously released ACh.
{"title":"The quantal catecholamine release from mouse chromaffin cells challenged with repeated ACh pulses is regulated by the mitochondrial Na+/Ca2+ exchanger","authors":"Ángela López-Gil, Carmen Nanclares, I. Méndez-López, Carmen Martínez-Ramírez, C. de los Ríos, J. F. Padín-Nogueira, M. Montero, L. Gandía, Antonio G. García","doi":"10.1113/JP273339","DOIUrl":"https://doi.org/10.1113/JP273339","url":null,"abstract":"Upon repeated application of short ACh pulses to C57BL6J mouse chromaffin cells, the amperometrically monitored secretory responses promptly decayed to a steady‐state level of around 25% of the initial response. A subsequent K+ pulse, however, overcame such decay. These data suggest that mouse chromaffin cells have a ready release‐vesicle pool that is selectively recruited by the physiological neurotransmitter ACh. The ACh‐sensitive vesicle pool is refilled and maintained by the rate of Ca2+ delivery from mitochondria to the cytosol, through the mitochondrial Na+/Ca2+ exchanger (mNCX). ITH12662, a novel blocker of the mNCX, prevented the decay of secretion elicited by ACh pulses and delayed the rate of [Ca2+]c clearance. This regulatory pathway may be physiologically relevant in situations of prolonged stressful conflicts where a sustained catecholamine release is regulated by mitochondrial Ca2+ circulation through the mNCX, which couples respiration and ATP synthesis to long‐term stimulation of chromaffin cells by endogenously released ACh.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"&NA; 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83450996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Yamaguchi, M. Steward, Kieran Smallbone, Y. Sohma, A. Yamamoto, S. Ko, T. Kondo, H. Ishiguro
The ductal system of the pancreas secretes large volumes of alkaline fluid containing HCO3− concentrations as high as 140 mm during hormonal stimulation. A computational model has been constructed to explore the underlying ion transport mechanisms. Parameters were estimated by fitting the model to experimental data from guinea‐pig pancreatic ducts. The model was readily able to secrete 140 mm HCO3−. Its capacity to do so was not dependent upon special properties of the cystic fibrosis transmembrane conductance regulator (CFTR) anion channels and solute carrier family 26 member A6 (SLC26A6) anion exchangers. We conclude that the main requirement for secreting high HCO3− concentrations is to minimize the secretion of Cl− ions. These findings help to clarify the mechanism responsible for pancreatic HCO3− secretion, a vital process that prevents the formation of protein plugs and viscous mucus in the ducts, which could otherwise lead to pancreatic disease.
{"title":"Bicarbonate‐rich fluid secretion predicted by a computational model of guinea‐pig pancreatic duct epithelium","authors":"M. Yamaguchi, M. Steward, Kieran Smallbone, Y. Sohma, A. Yamamoto, S. Ko, T. Kondo, H. Ishiguro","doi":"10.1113/JP273306","DOIUrl":"https://doi.org/10.1113/JP273306","url":null,"abstract":"The ductal system of the pancreas secretes large volumes of alkaline fluid containing HCO3− concentrations as high as 140 mm during hormonal stimulation. A computational model has been constructed to explore the underlying ion transport mechanisms. Parameters were estimated by fitting the model to experimental data from guinea‐pig pancreatic ducts. The model was readily able to secrete 140 mm HCO3−. Its capacity to do so was not dependent upon special properties of the cystic fibrosis transmembrane conductance regulator (CFTR) anion channels and solute carrier family 26 member A6 (SLC26A6) anion exchangers. We conclude that the main requirement for secreting high HCO3− concentrations is to minimize the secretion of Cl− ions. These findings help to clarify the mechanism responsible for pancreatic HCO3− secretion, a vital process that prevents the formation of protein plugs and viscous mucus in the ducts, which could otherwise lead to pancreatic disease.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80604842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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