You have free access to this content

The Journal of Physiology

Cover image for Vol. 588 Issue 20

October 2010

Volume 588, Issue 20

Pages 1–4055

  1. Issue Information

    1. Top of page
    2. Issue Information
    3. PERSPECTIVES
    4. JOURNAL CLUB
    5. NEUROSCIENCE
    6. CARDIOVASCULAR
    7. SKELETAL MUSCLE AND EXERCISE
    8. CORRIGENDUM
    1. You have free access to this content
      Issue Information (pages 1–5)

      Version of Record online: 14 OCT 2010 | DOI: 10.1113/jphysiol.2010.58820

  2. PERSPECTIVES

    1. Top of page
    2. Issue Information
    3. PERSPECTIVES
    4. JOURNAL CLUB
    5. NEUROSCIENCE
    6. CARDIOVASCULAR
    7. SKELETAL MUSCLE AND EXERCISE
    8. CORRIGENDUM
    1. You have free access to this content
    2. You have free access to this content
  3. JOURNAL CLUB

    1. Top of page
    2. Issue Information
    3. PERSPECTIVES
    4. JOURNAL CLUB
    5. NEUROSCIENCE
    6. CARDIOVASCULAR
    7. SKELETAL MUSCLE AND EXERCISE
    8. CORRIGENDUM
    1. You have free access to this content
      Altered microvascular control of exercising skeletal muscle blood flow: the unfortunate male? (pages 3851–3852)

      Emma C. Hart, Marcos G. Lopez and Darren P. Casey

      Version of Record online: 14 OCT 2010 | DOI: 10.1113/jphysiol.2010.195800

    2. You have free access to this content
      The specific origin of the simple and complex spikes in Purkinje neurons (page 3853)

      Eric Avila Orozco, Rodrigo Bolaños Jiménez, José Luis Calderón Álvarez-Tostado, William Vogt and Gerardo Rivera Silva

      Version of Record online: 14 OCT 2010 | DOI: 10.1113/jphysiol.2010.198325

  4. NEUROSCIENCE

    1. Top of page
    2. Issue Information
    3. PERSPECTIVES
    4. JOURNAL CLUB
    5. NEUROSCIENCE
    6. CARDIOVASCULAR
    7. SKELETAL MUSCLE AND EXERCISE
    8. CORRIGENDUM
    1. You have free access to this content
      Adaptation of the vestibulo-ocular reflex for forward-eyed foveate vision (pages 3855–3867)

      Americo A. Migliaccio, Lloyd B. Minor and Charles C. Della Santina

      Version of Record online: 14 OCT 2010 | DOI: 10.1113/jphysiol.2010.196287

      When the head turns unexpectedly, the vestibulo-ocular reflex turns the eyes the other way to keep gaze aligned with the target. Without this reflex, the visual world shifts when the head moves. In primates, this correction is precise (high gain) when the head turns left–right or up–down but is less precise (low gain) when the head tilts sideways. We show here that in the lateral-eyed afoveate chinchilla, these reflex corrections have equal gains in all directions. This points to an evolutionary adaptation of the primate reflex that is important for stereopsis while keeping the target image on the fovea to enhance acuity.

    2. You have free access to this content
      Flufenamic acid decreases neuronal excitability through modulation of voltage-gated sodium channel gating (pages 3869–3882)

      Hau-Jie Yau, Gytis Baranauskas and Marco Martina

      Version of Record online: 14 OCT 2010 | DOI: 10.1113/jphysiol.2010.193037

      Neuronal action potentials are generated by the interaction of two main voltage-gated conductances, one selectively permeable to sodium and the other to potassium ions. The gating properties of the ionic channels mediating these currents play a critical role in determining the threshold, frequency and shape of action potentials and therefore the modality of inter-neuronal communication. We studied the effects of flufenamic acid (FFA), a non-steroidal anti-inflammatory drug, on sodium channels. Our results show that FFA at near-clinical concentration has an inhibitory action on sodium currents. Biophysical analysis and computational simulations show that FFA acts by changing the voltage dependence of channels’ inactivation process. This effect heavily reduces the ability of neurons to discharge trains of action potentials, although the properties of individual action potentials are only slightly affected. The specific mode of action of FFA suggests that this molecule may be useful as anti-epileptic drug.

    3. You have free access to this content
      Developmental change in the electrophysiological and pharmacological properties of acid-sensing ion channels in CNS neurons (pages 3883–3900)

      Minghua Li, Eric Kratzer, Koichi Inoue, Roger P. Simon and Zhi-Gang Xiong

      Version of Record online: 14 OCT 2010 | DOI: 10.1113/jphysiol.2010.192922

      Acid-sensing ion channels (ASICs) are a novel family of ligand-gated ion channels activated by protons. Recent studies have demonstrated that activation of ASICs, particularly the calcium-permeable ASIC1a channels, plays an important role in the learning/memory process and in acidosis-mediated neuronal injury. In CNS neurons, ASIC1a and ASIC2a subunits are the major functional subunits where combinations of homomeric and heteromeric channels co-exist. Since ASIC1a and ASIC2a subunits have dramatic differences in their electrophysiological/pharmacological properties, any changes in the levels of individual subunits may have a significant influence on the properties of ASICs and their role in acid signalling. In this study, we demonstrate dramatic developmental changes in the electrophysiological and pharmacological properties of ASICs in CNS neurons, which are probably mediated by the change of expression level of ASIC subunits. Our findings may explain the age-dependent changes in learning/memory and the sensitivity of different age groups to acidosis-mediated neuronal injury.

    4. You have free access to this content
      Connexin hemichannel-mediated CO2-dependent release of ATP in the medulla oblongata contributes to central respiratory chemosensitivity (pages 3901–3920)

      Robert T. R. Huckstepp, Rachid Id Bihi, Robert Eason, K. Michael Spyer, Nikolai Dicke, Klaus Willecke, Nephtali Marina, Alexander V. Gourine and Nicholas Dale

      Version of Record online: 14 OCT 2010 | DOI: 10.1113/jphysiol.2010.192088

      The brain can detect CO2 in the blood and adjust our breathing so that the level of CO2, and hence the acidity of the blood, remains within physiological limits. Although the areas of the brain involved in detecting CO2 are known, we do not understand how CO2 is detected. We show that a connexin channel, Cx26, which often forms a passageway between cells, but in this case acts as a hemichannel that opens to the extracellular space, is expressed in glial cells of the CO2-sensing areas of the brain. Cx26 opens in proportion to the level of CO2 to release ATP, which then excites the neurons that control breathing. Our results identify a novel transducing mechanism for the detection of CO2 and suggest a hitherto unknown physiological function for Cx26 hemichannels.

    5. You have free access to this content
      CO2-dependent opening of connexin 26 and related β connexins (pages 3921–3931)

      Robert T. R. Huckstepp, Robert Eason, Anshu Sachdev and Nicholas Dale

      Version of Record online: 14 OCT 2010 | DOI: 10.1113/jphysiol.2010.192096

      We have previously shown that Cx26 plays an important role in the detection of CO2 and opens to allow the release of ATP, which excites neurons of the breathing network to mediate homeostatic control of the levels of CO2 in the blood. In this paper we study the properties of Cx26 and related connexins to see whether they can respond to changes in CO2 directly. A small number of evolutionarily close connexins respond to changes in CO2. Cx26 is particularly sensitive to CO2 over ranges that are relevant to the control of breathing and most likely responds directly to CO2 itself rather than through an intermediary. As Cx26 is widely distributed across the surface of the brain, it could play a role in a number of other CO2-sensitive processes such as control of blood flow through the brain.

    6. You have free access to this content
      Lithium acts as a potentiator of AMPAR currents in hippocampal CA1 cells by selectively increasing channel open probability (pages 3933–3941)

      Christine Gebhardt and Stuart G. Cull-Candy

      Version of Record online: 14 OCT 2010 | DOI: 10.1113/jphysiol.2010.195115

      Lithium has been used for more than 50 years to treat bipolar disorder worldwide. Remarkably, although lithium is effective, its site and mode of action are unknown. Information about this could provide insight that would benefit future treatments of mood disorders. We examined the effects of lithium, at clinically relevant concentrations, on AMPA type glutamate receptors in nerve cells. When activated by neurotransmitter (glutamate) these receptors mediate the majority of fast information transfers in the brain. Our experiments show that lithium potentiates certain subtypes of AMPA receptors. However, it does so in a way that appears to differ from certain other well studied AMPAR potentiators, which are thought to act by slowing down dissociation of the neurotransmitter from the receptor.

    7. You have free access to this content
      Fast glutamate uptake via EAAT2 shapes the cone-mediated light offset response in bipolar cells (pages 3943–3956)

      Matthew J. M. Rowan, Harris Ripps and Wen Shen

      Version of Record online: 14 OCT 2010 | DOI: 10.1113/jphysiol.2010.191437

      Glutamate is the main excitatory neurotransmitter in the retina and throughout the CNS, where its release from nerve terminals is essential for relaying signals between nerve cells. However, if allowed to accumulate in the synaptic cleft, it can result in prolonged activation of target cells, depletion within glutamatergic neurons, and neurotoxicity. These consequences are precluded by the presence of excitatory amino acid transporters (EAATs), which are responsible for the uptake of this amino acid into the neurons from which it is discharged. Using multiple techniques, we studied the functions of EAAT2, a subtype of glutamate transporter, in the synapse between photoreceptors and bipolar cells of the salamander retina. We found that presynaptic EAAT2A rapidly bound exocytosed glutamate, thereby limiting glutamate spillover to adjacent receptors at postsynaptic sites, and suppressing the rapid, transient glutamate signal from cones following light termination. Thus, EAAT2 preserves the cone signalling pathway in the distal retina.

  5. CARDIOVASCULAR

    1. Top of page
    2. Issue Information
    3. PERSPECTIVES
    4. JOURNAL CLUB
    5. NEUROSCIENCE
    6. CARDIOVASCULAR
    7. SKELETAL MUSCLE AND EXERCISE
    8. CORRIGENDUM
    1. You have free access to this content
      Tissue contribution to the mechanical features of diaphragmatic initial lymphatics (pages 3957–3969)

      Andrea Moriondo, Federica Boschetti, Francesca Bianchin, Simone Lattanzio, Cristiana Marcozzi and Daniela Negrini

      Version of Record online: 14 OCT 2010 | DOI: 10.1113/jphysiol.2010.196204

      The lymphatic system drains fluid, solutes and cells from the tissue and carries them back to the blood stream, thus maintaining a normal fluid volume and composition. In small initial lymphatics, originating directly from the tissue, lymph forms down pressure gradients developing between the tissue and the vessel lumen. We showed that lymph formation and progression may critically depend upon the mechanical properties of the tissue itself: vessels delimited by a compliant tissue serve as distensible reservoirs of drained interstitial fluid, while those surrounded by stiffer tissue more efficiently propel fluid along the lymphatic network. These results help us better understanding the lymphatic function and may therefore be useful in clarifying the mechanisms maintaining tissue fluid homeostasis and/or leading to its disturbances.

    2. You have free access to this content
      Arterial stiffening with ageing is associated with transforming growth factor-β1-related changes in adventitial collagen: reversal by aerobic exercise (pages 3971–3982)

      Bradley S. Fleenor, Kurt D. Marshall, Jessica R. Durrant, Lisa A. Lesniewski and Douglas R. Seals

      Version of Record online: 14 OCT 2010 | DOI: 10.1113/jphysiol.2010.194753

      Advancing age causes large arteries in the chest and neck to stiffen, which increases the chances of having a heart attack or stroke. Arteries are composed of two main extracellular proteins, collagen and elastin, which contribute to both the structure and the stiffness of vessels. Regular exercise decreases the stiffening of arteries with ageing. However, the specific location of the changes in collagen and elastin within the arteries with ageing that lead to stiffening and the effects of exercise are unknown. Here we show that reduced stiffness in older mice that exercise is largely due to reductions in collagen in the adventitial (outermost) layer of arteries. However, exercise had no effect on elastin content. These results increase our understanding of how these large arteries stiffen with old age and the processes by which regular exercise helps to prevent this.

    3. You have free access to this content
      Intravascular pressure augments cerebral arterial constriction by inducing voltage-insensitive Ca2+ waves (pages 3983–4005)

      Rania E. Mufti, Suzanne E. Brett, Cam Ha T. Tran, Rasha Abd El-Rahman, Yana Anfinogenova, Ahmed El-Yazbi, William C. Cole, Peter P. Jones, S.R. Wayne Chen and Donald G. Welsh

      Version of Record online: 14 OCT 2010 | DOI: 10.1113/jphysiol.2010.193300

      Tissue blood flow is controlled by a network of resistance arteries. Under normal conditions, the diameter of an artery is regulated by: (1) agents released from nerves and surrounding tissue; and (2) mechanical forces including blood pressure. Bayliss first described the ability of arteries to constrict to blood pressure and since his pioneering work in 1902, studies have been interested in defining the signalling events underlying this important biological response. Using a range of physiological and biochemical techniques, this study showed that Ca2+ waves play an important role in enabling arteries to respond to elevated blood pressure. Ca2+ waves are discrete events that spread in an asynchronous manner from one end of a smooth muscle cell to the other. These events depend on the release of Ca2+ from an internal store called the sarcoplasmic reticulum.

    4. You have free access to this content
      Coronary vasoconstrictor responses are attenuated in young women as compared with age-matched men (pages 4007–4016)

      Afsana Momen, Zhaohui Gao, Abigail Cohen, Tamreen Khan, Urs A. Leuenberger and Lawrence I. Sinoway

      Version of Record online: 14 OCT 2010 | DOI: 10.1113/jphysiol.2010.192492

      In animals, activation of the sympathetic nervous system during exercise causes epicardial coronary artery constriction. This effect helps maintain blood supply to the vulnerable inner layer of cardiac muscle during exercise. In humans, epicardial coronary artery constriction also occurs during handgrip exercise. In this report, we show that epicardial coronary artery constriction that occurs during exercise is greater in men than in women. We speculate that this coronary constriction in men but not in women helps maintain blood flow throughout all layers of cardiac muscle. Our results help us better understand the gender-related differences in cardiac muscle ischaemia than are seen in men and women.

    5. You have free access to this content
      Vasodilatory responsiveness to adenosine triphosphate in ageing humans (pages 4017–4027)

      Brett S. Kirby, Anne R. Crecelius, Wyatt F. Voyles and Frank A. Dinenno

      Version of Record online: 14 OCT 2010 | DOI: 10.1113/jphysiol.2010.197814

      The innermost lining of a blood vessel (endothelium) is important for increasing vessel diameter and facilitating increases in blood flow and oxygen delivery to muscle. This process is typically impaired in older adults. We demonstrate that increases in blood flow to the naturally circulating vessel relaxant, ATP, are intact in older adults who have an impaired innermost lining of muscle blood vessels. Our results show that an unhealthy endothelium does not always translate to an inability to relax blood vessels and aids in the overall understanding of how blood vessels control oxygen delivery to muscle as humans get older.

  6. SKELETAL MUSCLE AND EXERCISE

    1. Top of page
    2. Issue Information
    3. PERSPECTIVES
    4. JOURNAL CLUB
    5. NEUROSCIENCE
    6. CARDIOVASCULAR
    7. SKELETAL MUSCLE AND EXERCISE
    8. CORRIGENDUM
    1. You have free access to this content
      Muscle specific microRNAs are regulated by endurance exercise in human skeletal muscle (pages 4029–4037)

      Søren Nielsen, Camilla Scheele, Christina Yfanti, Thorbjörn Åkerström, Anders R. Nielsen, Bente K. Pedersen and Matthew Laye

      Version of Record online: 14 OCT 2010 | DOI: 10.1113/jphysiol.2010.189860

      MicroRNAs are small non-coding RNAs which negatively regulate gene expression. The muscle specific microRNAs (myomiRs) play an important role in muscle development, thus implicating a role for them in muscle adaptation to exercise. We show, in young healthy men, that endurance exercise alters the regulation of myomiRs and that predicted exercise target proteins partly follow the expression pattern of the myomiRs. We further demonstrate that the myomiR response to acute exercise differs from the long-term training response. While two out of four myomiRs increased in response to acute exercise, all four myomiRs decreased in response to 12 weeks of endurance training. Following 2 weeks of non-training, the myomiRs were back at the expression level observed before the training period. In contrast to a recently published study, we found no relation between insulin and myomiR expression. Our data contribute to the understanding of the complex mechanisms behind training adaption in human skeletal muscle.

      Corrected by:

      Corrigendum

      Vol. 589, Issue 5, 1239, Version of Record online: 25 FEB 2011

      Corrected by:

      Corrigenda: Corrigenda

      Vol. 593, Issue 5, 1323, Version of Record online: 26 FEB 2015

    2. You have free access to this content
      Chronic heart failure decreases cross-bridge kinetics in single skeletal muscle fibres from humans (pages 4039–4053)

      Mark S. Miller, Peter VanBuren, Martin M. LeWinter, Joan M. Braddock, Philip A. Ades, David W. Maughan, Bradley M. Palmer and Michael J. Toth

      Version of Record online: 14 OCT 2010 | DOI: 10.1113/jphysiol.2010.191957

      Chronic heart failure patients commonly experience skeletal muscle weakness, which hampers their ability to perform everyday tasks. Previous studies have found that this skeletal muscle weakness may be related to the loss of the contractile protein myosin. In this study, we applied a novel technique for the first time in single skeletal muscle fibres from humans to determine if myosin loss affected their contractile performance. Patients were found to have alterations in the biochemical properties of myosin, which counteract its depletion and result in similar tension generation compared to activity- and age-matched controls. Collectively, these results show that heart failure alters the functional properties of the myosin molecule, which may influence whole skeletal muscle function.

  7. CORRIGENDUM

    1. Top of page
    2. Issue Information
    3. PERSPECTIVES
    4. JOURNAL CLUB
    5. NEUROSCIENCE
    6. CARDIOVASCULAR
    7. SKELETAL MUSCLE AND EXERCISE
    8. CORRIGENDUM
    1. You have free access to this content
      Corrigendum (page 4055)

      Version of Record online: 14 OCT 2010 | DOI: 10.1113/jphysiol.2010.198820

      This article corrects:

      Mitochondrial respiration in subcutaneous and visceral adipose tissue from patients with morbid obesity

      Vol. 588, Issue 12, 2023–2032, Version of Record online: 14 JUN 2010

SEARCH

SEARCH BY CITATION