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The Journal of Physiology

Cover image for Vol. 588 Issue 19

October 2010

Volume 588, Issue 19

Pages 1–3845

  1. Issue Information

    1. Top of page
    2. Issue Information
    3. PERSPECTIVES
    4. TOPICAL REVIEWS
    5. MOLECULAR AND CELLULAR
    6. NEUROSCIENCE
    7. CARDIOVASCULAR
    8. RENAL AND ENDOCRINE
    9. SKELETAL MUSCLE AND EXERCISE
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      Issue Information (pages 1–5)

      Version of Record online: 30 SEP 2010 | DOI: 10.1113/jphysiol.2010.58819

  2. PERSPECTIVES

    1. Top of page
    2. Issue Information
    3. PERSPECTIVES
    4. TOPICAL REVIEWS
    5. MOLECULAR AND CELLULAR
    6. NEUROSCIENCE
    7. CARDIOVASCULAR
    8. RENAL AND ENDOCRINE
    9. SKELETAL MUSCLE AND EXERCISE
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      Insulin: a sweet deal for human baroreflex function (page 3629)

      Virginia L. Brooks

      Version of Record online: 30 SEP 2010 | DOI: 10.1113/jphysiol.2010.197830

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      Under pressure – Kv channels and myogenic control of cerebral blood flow (pages 3635–3636)

      Shaun L. Sandow and Timothy V. Murphy

      Version of Record online: 30 SEP 2010 | DOI: 10.1113/jphysiol.2010.197996

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  3. TOPICAL REVIEWS

    1. Top of page
    2. Issue Information
    3. PERSPECTIVES
    4. TOPICAL REVIEWS
    5. MOLECULAR AND CELLULAR
    6. NEUROSCIENCE
    7. CARDIOVASCULAR
    8. RENAL AND ENDOCRINE
    9. SKELETAL MUSCLE AND EXERCISE
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      Discovery and rediscoveries of Golgi cells (pages 3639–3655)

      Elisa Galliano, Paolo Mazzarello and Egidio D’Angelo

      Version of Record online: 30 SEP 2010 | DOI: 10.1113/jphysiol.2010.189605

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  4. MOLECULAR AND CELLULAR

    1. Top of page
    2. Issue Information
    3. PERSPECTIVES
    4. TOPICAL REVIEWS
    5. MOLECULAR AND CELLULAR
    6. NEUROSCIENCE
    7. CARDIOVASCULAR
    8. RENAL AND ENDOCRINE
    9. SKELETAL MUSCLE AND EXERCISE
    1. RAPID REPORT

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      TRPC6 channels stimulated by angiotensin II are inhibited by TRPC1/C5 channel activity through a Ca2+- and PKC-dependent mechanism in native vascular myocytes (pages 3671–3682)

      J. Shi, M. Ju, S. N. Saleh, A. P. Albert and W. A. Large

      Version of Record online: 30 SEP 2010 | DOI: 10.1113/jphysiol.2010.194621

      The walls of blood vessels contain muscle cells that contract to make vessels become narrower, which contributes to an increase in blood pressure. Proteins found in the outer surface of these muscle cells, called TRPC channels, are important for initiating muscle contraction. In the present work, we show that angiotensin II, an important chemical involved in controlling blood pressure, activates two types of TRPC channels called TRPC1/C5 and TRPC6 in these vascular muscle cells. Our new findings show that activation of TRPC1/C5 channels causes Ca2+ ions to enter the muscle cells and activate an enzyme, protein kinase C, which inhibits the activity of the TRPC6 channels. These results show for the first time that different TRPC channels can regulate the activity of each other, which is an important discovery in understanding how blood vessels produce contraction and control blood pressure.

  5. NEUROSCIENCE

    1. Top of page
    2. Issue Information
    3. PERSPECTIVES
    4. TOPICAL REVIEWS
    5. MOLECULAR AND CELLULAR
    6. NEUROSCIENCE
    7. CARDIOVASCULAR
    8. RENAL AND ENDOCRINE
    9. SKELETAL MUSCLE AND EXERCISE
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      Reversal of plasticity-like effects in the human motor cortex (pages 3683–3693)

      Ying-Zu Huang, John C. Rothwell, Chin-Song Lu, Wen-Li Chuang, Wey-Yil Lin and Rou-Shayn Chen

      Version of Record online: 30 SEP 2010 | DOI: 10.1113/jphysiol.2010.191361

      Plasticity describes the fact that the nervous system, in particularly the brain, is flexible in response to internal and external demands. This flexibility arises because connections between circuits can be potentiated or depressed, thus allowing the system to learn new tasks, or to re-organise after injury. In animal studies, such potentiation/depression can be reproduced by artificial stimulation of nerve pathways; importantly, it can be abolished by a second mild stimulation applied within a certain time window after the plasticity is induced. Behaviourally this might correspond to the fact that it is easier to reverse bad habits if we act before they stabilise, whereas it is much more difficult at a later time. Protocols to test early reversal of plasticity have never been demonstrated experimentally in conscious humans. The present experiments identify a possible method to investigate reversal of plasticity in the human brain using transcranial magnetic stimulation of the motor cortex.

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      Long-term inactivation particle for voltage-gated sodium channels (pages 3695–3711)

      Katarzyna Dover, Sergio Solinas, Egidio D’Angelo and Mitchell Goldfarb

      Version of Record online: 30 SEP 2010 | DOI: 10.1113/jphysiol.2010.192559

      Action potential generation is governed by the opening, inactivation and recovery of voltage-gated sodium channels. A channel's fast inactivation particle mediates both onset of inactivation upon membrane depolarization and rapid recovery upon repolarization. We describe here a novel inactivation particle housed within an accessory channel subunit (A-type FHF protein) mediating rapid-onset, long-term inactivation of several sodium channels. The channel-intrinsic and tethered FHF-derived particles compete for induction of inactivation, causing channels to progressively accumulate into the long-term refractory state during multiple depolarization cycles. A short peptide corresponding to the FHF particle can reproduce channel long-term inactivation and inhibit repetitive firing of cerebellar granule neurons. We discuss potential roles of A-type FHFs in the modulation of action potential generation and conduction, and the potential use of small molecules that mimic the FHF peptide particle in managing clinical disorders of cellular hyperexcitability.

      Corrected by:

      Errata

      Vol. 589, Issue 6, 1505, Version of Record online: 14 MAR 2011

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      P2Y1 receptors mediate an activation of neuronal calcium-dependent K+ channels (pages 3713–3725)

      Klaus W. Schicker, Giri K. Chandaka, Petra Geier, Helmut Kubista and Stefan Boehm

      Version of Record online: 30 SEP 2010 | DOI: 10.1113/jphysiol.2010.193367

      ADP and ATP not only provide an intracellular energy storage system, but are also released from neurons and other cells as signalling molecules. In the nervous system, ATP mediates fast synaptic transmission by activating ATP-gated ion channels, called P2X receptors. In addition, ATP and ADP activate another class of receptors, called P2Y, which mediate diverse effects in the nervous system through complex intracellular signalling cascades. Such signalling cascades often target voltage-gated ion channels and thereby change the excitability of a neuron. Here, we identify Ca2+-dependent potassium channels as novel targets for P2Y receptor associated signalling cascades. Since the gating of such channels critically determines the activity of a neuron and thus of the nervous system, our observations form the mechanistic basis for the roles of ATP and ADP in various brain functions.

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      Cholinergic modulation of excitatory synaptic input integration in hippocampal CA1 (pages 3727–3742)

      A. Rory McQuiston

      Version of Record online: 30 SEP 2010 | DOI: 10.1113/jphysiol.2010.188581

      The hippocampal region of the mammalian brain is involved in the formation of long-term memories. During memory formation the hippocampus displays oscillatory activity called the theta rhythm. The theta rhythm provides a mechanism for neuronal activity coming into the hippocampus to be integrated for subsequent long-term memory storage. The theta rhythm is partially dependent on the release of a neurotransmitter into the hippocampus called acetylcholine. Here I show that acetylcholine can differentially affect the integration of different types of neuronal activity within the hippocampus on the time scale of the theta rhythm.

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      Modulation of single-channel properties of TRPV1 by phosphorylation (pages 3743–3756)

      Milena Studer and Peter A. McNaughton

      Version of Record online: 30 SEP 2010 | DOI: 10.1113/jphysiol.2010.190611

      TRPV1 is an ion channel that is activated by heat and allows charge, in the form of positive ions, to cross nerve cell membranes and so excite the nerve. Inflammation or injury make TRPV1 open more readily, and so heat seems more painful when applied to injured areas. We recording the current passing through single TRPV1 channels, and used capsaicin (from chilli peppers) to activate TRPV1. We analysed the kinetics of channel opening and closing, and found that the channel moves through several ‘closed’ states of different durations before making the transition to one of several ‘open’ states. We found that TRPV1 opened more readily (open states were favoured) when we activated protein kinase C, which attaches a phosphate group to specific amino acids in TRPV1. These results help us understand how inflammation increases the sensation of pain, and may assist in the future development of novel analgesics.

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      Encoding of whisker input by cerebellar Purkinje cells (pages 3757–3783)

      Laurens W. J. Bosman, Sebastiaan K. E. Koekkoek, Joël Shapiro, Bianca F. M. Rijken, Froukje Zandstra, Barry Van Der Ende, Cullen B. Owens, Jan-Willem Potters, Jornt R. De Gruijl, Tom J. H. Ruigrok and Chris I. De Zeeuw

      Version of Record online: 30 SEP 2010 | DOI: 10.1113/jphysiol.2010.195180

      The rodent whisker system, combining simple movements with prompt sensory feedback, is generally considered as a model system to study integration of sensory and motor information. Although the cerebellum is critically important for this ‘sensorimotor integration’, hardly any functional data on its whisker representation is available. We show that Purkinje cells, which form the sole output of the cerebellar cortex, cooperate in functional groups to encode the amplitude, speed and direction of mechanical whisker stimulations. The two nervous pathways conveying input to the cerebellar cortex, the mossy fibre and the climbing fibre pathway, mediate different aspects of sensory input. Specifically, mossy fibre inputs convey information from multiple whiskers and are insensitive to the direction of whisker movement, while climbing fibres encode in a direction-specific way the movement of a single whisker. Thus, this study contributes to our understanding of how sensory input is distributed over and encoded by the cerebellar cortex.

  6. CARDIOVASCULAR

    1. Top of page
    2. Issue Information
    3. PERSPECTIVES
    4. TOPICAL REVIEWS
    5. MOLECULAR AND CELLULAR
    6. NEUROSCIENCE
    7. CARDIOVASCULAR
    8. RENAL AND ENDOCRINE
    9. SKELETAL MUSCLE AND EXERCISE
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      Prolonged ischaemia impairs muscle blood flow and oxygen uptake dynamics during subsequent heavy exercise (pages 3785–3797)

      Azmy Faisal, Kenneth S. Dyson and Richard L. Hughson

      Version of Record online: 30 SEP 2010 | DOI: 10.1113/jphysiol.2010.188698

      At the start of exercise a number of chemical pathways in the muscle cell are engaged to supply energy demand to the contractile muscle fibres. The preferred energy production pathway (oxidative phosphorylation) is dependent on a steady supply of oxygen and greater oxygen utilization in the exercising muscles. We increased the oxygen supply at the start of heavy hand-grip exercise via elevated muscle blood flow by prior heavy warm-up exercise and prior 15 min of forearm circulatory occlusion. Exercise performance during a heavy hand-grip exercise bout was enhanced only by prior heavy warm-up exercise but not prior prolonged circulatory occlusion that impaired the oxygen supply and utilization through the first minutes of exercise.

      Corrected by:

      Corrigendum: Corrigendum

      Vol. 594, Issue 7, 1957, Version of Record online: 9 MAR 2016

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      α-Adrenergic vasoconstrictor responsiveness is preserved in the heated human leg (pages 3799–3808)

      David M. Keller, Mikael Sander, Bente Stallknecht and Craig G. Crandall

      Version of Record online: 30 SEP 2010 | DOI: 10.1113/jphysiol.2010.194506

      Heat stress reduces one's ability to regulate blood pressure. Previous findings indicate a heat-induced reduction in the responsiveness of receptors that cause blood vessel constriction (i.e. α-adrenergic receptors) in the skin. Understanding the consequence of increased temperature on α-adrenergic receptors in the blood vessels of the whole leg and in leg skeletal muscle may provide important insight into the heat-induced reduction in blood pressure regulation. We demonstrated that isolated heating of one leg resulted in no change in whole-leg or leg skeletal muscle α-adrenergic receptor responsiveness. Additionally, leg heating increased baseline skeletal muscle blood flow.

  7. RENAL AND ENDOCRINE

    1. Top of page
    2. Issue Information
    3. PERSPECTIVES
    4. TOPICAL REVIEWS
    5. MOLECULAR AND CELLULAR
    6. NEUROSCIENCE
    7. CARDIOVASCULAR
    8. RENAL AND ENDOCRINE
    9. SKELETAL MUSCLE AND EXERCISE
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      Prenatal protein restriction leads to a disparity between aortic and peripheral blood pressure in Wistar male offspring (pages 3809–3818)

      Angelina Swali, Sarah McMullen and Simon C. Langley-Evans

      Version of Record online: 30 SEP 2010 | DOI: 10.1113/jphysiol.2010.194928

      Feeding a low protein diet throughout pregnancy results in hypertension of the adult offspring. In rodents, blood pressure is measured at the tail while the animal is restrained and therefore stressed, confounding the effects of prenatal diet. Radiotelemetry allows measurements from the aorta in free moving animals. This study measured blood pressure by both methods, simultaneously, in male Wistar rats following exposure to either control or low protein diets in utero. Blood pressure was increased in low protein rats when measured at the tail, but decreased in the aorta. Stress associated with tail pulsation measurements resulted in a similar blood pressure increase in both groups of animals. This eliminates the theory that prenatal protein restriction leads to a heightened stress response, alternatively suggesting that peripheral vascular resistance may be increased in these animals.

  8. SKELETAL MUSCLE AND EXERCISE

    1. Top of page
    2. Issue Information
    3. PERSPECTIVES
    4. TOPICAL REVIEWS
    5. MOLECULAR AND CELLULAR
    6. NEUROSCIENCE
    7. CARDIOVASCULAR
    8. RENAL AND ENDOCRINE
    9. SKELETAL MUSCLE AND EXERCISE
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      Is the efficiency of mammalian (mouse) skeletal muscle temperature dependent? (pages 3819–3831)

      C. J. Barclay, R. C. Woledge and N. A. Curtin

      Version of Record online: 30 SEP 2010 | DOI: 10.1113/jphysiol.2010.192799

      Human limb muscles seem to be more efficient than one would expect from studies of muscles from other mammalian species. That is, human muscles use less energy for each unit of mechanical work produced. It is possible that the difference between human and non-human muscle efficiencies is that non-human muscle is typically studied in vitro at temperatures below body temperature. This study investigated whether the efficiency of non-human mammalian muscle (from the mouse) depends on temperature. It was found that temperature has little effect on efficiency so this cannot account for the higher efficiency of human muscles. However, it is also likely that the difference in efficiency between human muscles and those of other mammals is smaller than previously suggested. The results are important because, although they don't explain why the efficiencies are different, they do suggest that fundamental processes that determine muscle efficiency are similar across mammalian species.

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      The effect of passive movement training on angiogenic factors and capillary growth in human skeletal muscle (pages 3833–3845)

      B. Høier, N. Rufener, J. Bojsen-Møller, J. Bangsbo and Y. Hellsten

      Version of Record online: 30 SEP 2010 | DOI: 10.1113/jphysiol.2010.190439

      Exercise training leads to many adaptations in the skeletal muscle that improve its function. One is growth of the smallest blood vessels, capillaries. These allow for oxygen and nutrients carried by the blood to reach the muscle cells. Our intention with this study was to determine whether 90 min of passive movement of the lower leg three times per week for 4 weeks would lead to growth of capillaries in the muscle. The results show that such passive movement of the leg enhances blood flow, stretches the muscle and leads to stimulation of capillary growth. This finding is important for our understanding of what makes capillaries grow and may help patients with cardiovascular disease.

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