The Japanese journal of physiology最新文献

{"title":"The substantia nigra modulates proximal colon tone and motility in a vagally-dependent manner in the rat.","authors":"Tiaosi Xing, G. Nanni, Cameron R Burkholder, K. Browning, R. Travagli","doi":"10.1152/physiol.2023.38.s1.5733721","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5733721","url":null,"abstract":"A monosynaptic pathway connects the substantia nigra pars compacta (SNpc) to neurons of the dorsal motor nucleus of the vagus (DMV). This monosynaptic pathway modulates the vagal control of gastric motility. It is not known, however, whether this nigro-vagal pathway also modulates the tone and motility of the proximal colon. In rats, microinjection of retrograde tracers in the proximal colon and of anterograde tracers in SNpc showed that bilaterally labelled colonic-projecting neurons in the DMV received inputs from SNpc neurons. Microinjections of the ionotropic glutamate receptor agonist, NMDA, in the SNpc increased proximal colonic motility and tone, as measured via a strain gauge aligned with the colonic circular smooth muscle; the motility increase was inhibited by acute subdiaphragmatic vagotomy. Upon transfection of SNpc with pAAV-hSyn-hM3D(Gq)-mCherry, chemogenetic activation of nigro-vagal nerve terminals by brainstem application of clozapine-N-oxide increased the firing rate of DMV neurons and proximal colon motility; both responses were abolished by brainstem pretreatment with the dopaminergic D1-like antagonist SCH23390. Chemogenetic inhibition of nigro-vagal nerve terminals following SNpc transfection with pAAV-hSyn-hM4D(Gi)-mCherry decreased the firing rate of DMV neurons and inhibited proximal colon motility. These data suggest that a nigro-vagal pathway modulates activity of the proximal colon motility tonically via a discrete dopaminergic synapse in a manner dependent on vagal efferent nerve activity. Impairment of this nigro-vagal pathway may contribute to the severely reduced colonic transit and prominent constipation observed in both patients and animal models of parkinsonism. KEY POINTS: Substantia nigra pars compacta (SNpc) neurons are connected to the dorsal motor nucleus of the vagus (DMV) neurons via a presumed direct pathway. Brainstem neurons in the lateral DMV innervate the proximal colon. Colonic-projecting DMV neurons receive inputs from neurons of the SNpc. The nigro-vagal pathway modulates tone and motility of the proximal colon via D1-like receptors in the DMV. The present study provides the mechanistic basis for explaining how SNpc alterations may lead to a high rate of constipation in patients with Parkinson's Disease.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"73 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80449007","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}

{"title":"Motor unit dysregulation following 15 days of unilateral lower limb immobilisation","authors":"T. Inns, J. Bass, E. Hardy, D. Stashuk, P. Atherton, B. Phillips, M. Piasecki","doi":"10.1101/2022.06.01.494421","DOIUrl":"https://doi.org/10.1101/2022.06.01.494421","url":null,"abstract":"Disuse atrophy, caused by situations of unloading such as limb immobilisation, causes a rapid yet diverging reduction in skeletal muscle function compared to muscle mass. While mechanistic insight into the loss of mass is well studied, deterioration of muscle function with a focus towards the neural input to muscle remains underexplored. This study aimed to determine the role of motor unit adaptation in disuse-induced neuromuscular deficits. 10 young, healthy male volunteers underwent 15 days of unilateral lower limb immobilisation. Intramuscular EMG (iEMG) was recorded from the vastus lateralis during knee extensor contractions normalised to maximal voluntary contraction (MVC) pre and post disuse-induced loss of function. Muscle cross-sectional area was determined by ultrasound. Individual MUs were sampled and analysed for changes in discharge characteristics and MU potential (MUP) shape and structure. Vastus lateralis CSA was reduced by approximately 15% which was exceeded by a two-fold decrease of 31% in muscle strength in the immobilised limb, with no change to the non-immobilised. Parameters of MUP size were largely reduced, while neuromuscular junction (NMJ) transmission instability increased at several contraction levels and MU firing rate reduced. All adaptations were observed in the immobilised limb only. These findings highlight impaired neural input following immobilisation reflected by suppressed MU discharge rate and instability of transmission at the NMJ which may underpin the disproportionate reductions of strength relative to muscle size.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"89 1","pages":"4753 - 4769"},"PeriodicalIF":0.0,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91458845","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}

{"title":"Persistent inward currents in spinal motoneurones: how can we study them in human participants?","authors":"Jacob R. Thorstensen","doi":"10.1113/JP283249","DOIUrl":"https://doi.org/10.1113/JP283249","url":null,"abstract":"Activation of a motoneurone occurs when excitatory synaptic input from descending motor pathways, or sensory projections, is sufficient to bring the membrane potential of the motoneurone above its firing threshold. The input–output gain of motoneurones is enhanced by monoamine neuromodulators released from raphe-spinal neurons (serotonin, 5-HT) and locus coeruleus neurons (noradrenaline, NA). These pathways form monosynaptic connections with the dendrites of motoneurones and have multiple effects on motoneurone excitability. Notably, 5-HT and NA have strong facilitation effects on voltage-gated persistent inward currents (PICs), which amplify synaptic input and promote the self-sustained discharge of motoneurones. In animal preparations with restricted neuromodulator release, intracellular recordings of motoneurones reveal that increasing the magnitude of injected current increases discharge rate linearly. However, in the presence of neuromodulation and PIC activation, the relationship between injected current and discharge rate becomes non-linear. This is reflected in the hysteresis between the magnitude of injected current needed for recruitment and at de-recruitment, one of many PIC-induced non-linearities (e.g. acceleration of firing, firing rate saturation). Compared to recruitment, injected current is lower at de-recruitment as less excitatory input is needed tomaintain ongoingmotoneurone discharge as PICs are active and are generating a strong intrinsic depolarization. Human motoneurones also exhibit hysteresis in the amount of excitatory drive needed to recruit compared to de-recruitment. Instead of injecting current to cause recruitment and de-recruitment, voluntary isometric contractions can be performed to activate motoneurones via synaptic input, and the magnitude of synaptic activation can be inferred from motor unit discharge recorded with electromyography (EMG). Specifically, the discharge rate of a voluntarily recruited lower-threshold ‘control’ unit can be used as an estimate of net synaptic input to the motoneurone pool and a higher-threshold ‘test’ unit. The difference in firing rates for the control unit at the time of recruitment and de-recruitment of the test unit (delta frequency, F) is used to determine the contribution of PICs to test unit activation, with smaller differences indicating a smaller contribution of PICs to motoneurone activation (Gorassini et al., 2002). Animal preparations indicate that the amplitude of PICs in motoneurones is directly proportional to neuromodulatory drive (Heckman et al., 2009), and hence estimating PIC amplitude with the paired motor unit technique provides an opportunity to study the neuromodulatory control of human motoneurones. Neuromodulatory drive to the spinal cord is dynamic, whereby the amount of monoamine release depends on certain behaviours. 5-HT release is coupled with the intensity of motor activity, where higher-intensity motor activities result in more release. NA release t","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76211597","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}

{"title":"Concurrent exposure to (acute intermittent) hypoxia and hypercapnia: a promising therapeutic cocktail for neuroplasticity?","authors":"R. Mesquita","doi":"10.1113/JP283215","DOIUrl":"https://doi.org/10.1113/JP283215","url":null,"abstract":"(peripheral chemoreceptor activation) raphe-spinal serotonergic activation of the serotonergic chemoreceptor activation).","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"58 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84867080","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}

{"title":"Remote ischaemic preconditioning – translating cardiovascular benefits to humans","authors":"J. Lang, Jahyun Kim","doi":"10.1113/JP282568","DOIUrl":"https://doi.org/10.1113/JP282568","url":null,"abstract":"Remote ischaemic preconditioning (RIPC), induced by intermittent periods of limb ischaemia and reperfusion, confers cardiac and vascular protection from subsequent ischaemia–reperfusion (IR) injury. Early animal studies reliably demonstrate that RIPC attenuated infarct size and preserved cardiac tissue. However, translating these adaptations to clinical practice in humans has been challenging. Large clinical studies have found inconsistent results with respect to RIPC eliciting IR injury protection or improving clinical outcomes. Follow‐up studies have implicated several factors that potentially affect the efficacy of RIPC in humans such as age, fitness, frequency, disease state and interactions with medications. Thus, realizing the clinical potential for RIPC may require a human experimental model where confounding factors are more effectively controlled and underlying mechanisms can be further elucidated. In this review, we highlight recent experimental findings in the peripheral circulation that have added valuable insight on the mechanisms and clinical benefit of RIPC in humans. Central to this discussion is the critical role of timing (i.e. immediate vs. delayed effects following a single bout of RIPC) and the frequency of RIPC. Limited evidence in humans has demonstrated that repeated bouts of RIPC over several days uniquely improves vascular function beyond that observed with a single bout alone. Since changes in resistance vessel and microvascular function often precede symptoms and diagnosis of cardiovascular disease, repeated bouts of RIPC may be promising as a preclinical intervention to prevent or delay cardiovascular disease progression.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"533 1","pages":"3053 - 3067"},"PeriodicalIF":0.0,"publicationDate":"2022-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89351887","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}

{"title":"Welcome to the touch dome!","authors":"V. Macefield","doi":"10.1113/JP282866","DOIUrl":"https://doi.org/10.1113/JP282866","url":null,"abstract":"ThisHistorical Perspective article celebrates the 600th volume of The Journal of Physiology, recognizing the most highly cited papers published in the Journal. Here I discuss the significance of a landmark study published in 1969 by Ainsley Iggo and Alan Muir, from the Departments of Anatomy and Physiology at The University of Edinburgh. A graduate of Otago University in New Zealand, and having received training in neurophysiology under the tutelage of Jack Eccles, Iggo arrived in Edinburgh (after a 2-year stint in Aberdeen) in 1952 (Iggo, 2001). The paper of interest here, titled The structure and function of a slowly adapting touch corpuscle in hairy skin, built on his work with Muir (his student) in which they had characterized the ‘touch dome’ mechanoreceptors in the hairy skin of the cat. After shaving the hairy skin these domes can be readily seen as punctate elevations of the epidermis, which are usually (but not always) associated with a single hair. The sensory axons that supply these endings are known as the slowly adapting type I (SAI) afferents, and histological evidence showed that the mechanoreceptors are the Merkel cell receptors, now known asMerkel cell–neurite complexes. SAI afferents possess small, well-defined receptive fields composed of several ‘hot spots.’ Iggo and Muir showed that each touch dome is innervated by a single myelinated axon that branches to end as Merkel discs, although a given parent axon can supply several touch domes. Subsequent work in humans, in which single-unit recordings were made via tungsten microelectrodes inserted into the lateral antebrachial cutaneous nerve, demonstrated that the receptive fields of SAI afferents in hairy skin are composed of two to four ‘hot spots’ of maximal sensitivity, each no doubt corresponding to the location of the receptor terminal from a single axon that branches from the parent axon (Vallbo et al., 1995). In the glabrous skin of the hand there are no touch domes; here, the Merkel cell–neurite complexes are associated with the patterned elevations of the epidermis that form the fingerprint ridges. Nevertheless, the receptive fields of these SAI afferents are composed of several distinct subfields spread across multiple ridges, such that the receptor endings underlying each of these ‘hot spots’ can detect mechanical events at individual fingerprint ridges (Jarocka et al., 2021). Iggo and Muir performed an extensive analysis of the physiology of the ‘touch spot’ receptors. Earlier studies by Brown and Iggo (1963) demonstrated that, after crushing the parent nerve, the characteristic slowly adapting discharge of the afferent only returned once the axon had regrown into the touch dome and the Merkel cell complex had reformed. Iggo and Muir showed that while the receptors responded well to punctate indentation of the touch dome, they were particularly sensitive to light stroking across the receptive field, a feature exhibited by SAI afferents recorded in humans. And, like hu","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"05 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86109821","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}

{"title":"Ion Channels","authors":"D. Lipscombe, C. Toro","doi":"10.1113/jphysiol.1997.sp021990","DOIUrl":"https://doi.org/10.1113/jphysiol.1997.sp021990","url":null,"abstract":"","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80845268","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}

{"title":"Home exercise reduces cardiometabolic disease risk","authors":"Cesar A Meza","doi":"10.1113/JP278934","DOIUrl":"https://doi.org/10.1113/JP278934","url":null,"abstract":"Obesity and a sedentary lifestyle are major contributors to poor metabolic and vascular health. As such, there has been a focus towards understanding the mechanisms underlying improvements in health related to physical activity. However, there remains a need for strategies that encourage patients to perform exercise independently and outside of the laboratory-supervised research setting. Investigations into skeletal muscle microvasculature function can provide insight into the links between cardiovascular and metabolic health. Increased nitric oxide (NO) production via endothelial NO synthase (eNOS) promotes muscle capillary recruitment to increase insulin-stimulated glucose uptake (Vincent et al. 2004). However, the levels of bioavailable NO are reduced in obesity due to quenching by oxidants, such as superoxide. NADPH oxidase (NOX) complexes are predominant sources of superoxide in the endothelium of obese individuals; therefore, the relative activation of eNOS versus NOX may provide an indication of microvascular function. In a recent issue of The Journal of Physiology, Scott et al. (2019) investigated whether home-based exercise can mitigate insulin resistance and vascular dysfunction while eliminating potential barriers of exercise adherence, such as access to facilities. Thirty-two males and females (age 36 ± 10 years) with an elevated risk of developing cardiovascular disease (body mass index 34.3 ± 5 kg/m; V̇O2peak 24.6 5.7 ml/kg/min) performed 12 weeks of exercise training under one of the following conditions: home-based high-intensity interval training (Home-HIT; n = 9), laboratory-based supervised HIT (Lab-HIT; n = 10) or home-based moderate-intensity continuous training (Home-MICT; n = 13). The participants who performed home-based exercise were ‘virtually supervised’ using a heart rate monitor, and instructed to achieve 80% or 65% of predicted heart rate maximum (HRmax 220 – age) during the intervals or continuous exercise, respectively. The home-based and laboratory-supervised HIT exercise sessions consisted of 1-min bouts of exercise interspersed with 1 min of rest. The Home-MICT group was instructed to perform continuous exercise of either swimming, cycling or walking/running. Participants in each group trained three times per week. To monitor adherence to exercise prescription, HR data obtained from the HR monitors were automatically uploaded to a cloud storage site (www.flow.polar.com) after each session. Endothelial function and aortic stiffness were assessed via flow-mediated dilatation (FMD) and pulse wave velocity (PWV), respectively. Insulin sensitivity was measured using an oral glucose tolerance test (OGTT). Lastly, a resting muscle biopsy was collected to measure markers of metabolic and vascular function via immunofluorescence. The primary finding was that the improvements in endothelium-dependent dilatation, aortic stiffness and insulin sensitivity were comparable between home-based exercise groups and laboratory-supe","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"73 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89895318","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}

{"title":"In Memoriam: Paul M. Vanhoutte.","authors":"M. Barton, C. Cardillo","doi":"10.1113/JP279124","DOIUrl":"https://doi.org/10.1113/JP279124","url":null,"abstract":"On 23 August 2019, science lost one of its great minds: Paul Michel Georges Remi Vanhoutte, born on 26 November 1940 in Merelbeke near Ghent in Belgium, unexpectedly died in Paris after he had suffered a fall 10 days earlier. He was ‘one of the fathers of vascular biology’ (Heistad, 2008) who contributed to and shaped our understanding of how vascular endothelial cells regulate blood flow under physiological conditions and in disease.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"183 1","pages":"5731-5737"},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83454523","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}

{"title":"Keeping mitochondria happy – benefits of a pore choice in acute pancreatitis","authors":"D. Criddle","doi":"10.1113/JP279116","DOIUrl":"https://doi.org/10.1113/JP279116","url":null,"abstract":"Mitochondrial dysfunction is a key feature of multiple diseases and thus protection of this organelle is an important therapeutic objective. The pancreatic acinar cell, which synthesises and stores digestive enzyme precursors, is the most abundant cell type in pancreatic tissue and considered to be the primary site of acute pancreatitis (AP) initiation. Early investigations at the University of Liverpool and by others discovered that precipitants of AP, including bile acids and alcohol non‐oxidative metabolites, disrupt calcium signalling in acinar cells leading to toxicity. Sustained cytosolic calcium elevations raise mitochondrial matrix calcium, triggering the opening of the mitochondrial permeability transition pore (MPTP), which results in a loss of membrane potential and ATP production vital for cellular processes (Criddle et al . 2006; Mukherjee et al . 2016) (Fig. 1). The prime consequence of pancreatic mitochondrial dysfunction in AP is necrotic cell death, the extent of which is a major determinant of clinical outcome. Subsequent studies have shown that calcium‐dependent mitochondrial dysfunction in response to AP precipitants also occurs in ductal cells, widening the cast of players implicated in the development of AP (Hegyi & Petersen, 2013). There is currently no specific therapy for the disease and protection of mitochondria by MPTP inhibition is considered a promising therapeutic approach.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"78 1","pages":"5741 - 5742"},"PeriodicalIF":0.0,"publicationDate":"2019-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76089829","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}