Current Issue

Volume 588 Issue 3 (February 2010)

EDITORIALS

The Journal of Physiology Annual Report 2009 (p 387-389)
William A. Large, Carol Huxley
Published Online: Jan 29 2010 3:21AM
DOI: 10.1113/jphysiol.2009.185769

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PERSPECTIVES

Stress synchronizes calcium release and promotes SR calcium leak (p 391-392)
Wei Wang, Xander H. T. Wehrens
Published Online: Jan 29 2010 3:21AM
DOI: 10.1113/jphysiol.2009.184978

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'Placental programming': more may still be less (p 393-393)
Pawel Borowicz, Lawrence P. Reynolds
Published Online: Jan 29 2010 3:21AM
DOI: 10.1113/jphysiol.2009.185983

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JOURNAL CLUB

Growing collagen, not muscle, with weightlifting and 'growth' hormone (p 395-396)
Nicholas A. Burd, Daniel W. D. West, Tyler A. Churchward-Venne, Cameron J. Mitchell
Published Online: Jan 29 2010 3:21AM
DOI: 10.1113/jphysiol.2009.185306

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Rethinking the role of superoxide in the ageing skeletal muscle vasculature (p 397-398)
Daniel W. Trott, John W. Seawright
Published Online: Jan 29 2010 3:21AM
DOI: 10.1113/jphysiol.2009.183939

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NEUROSCIENCE

Calcium activity in different classes of myenteric neurons underlying the migrating motor complex in the murine colon (p 399-421)
Peter O. Bayguinov, Grant W. Hennig, Terence K. Smith
Published Online: Jan 29 2010 3:21AM
DOI: 10.1113/jphysiol.2009.181172

Non-technical summary
The spontaneous colonic migrating motor complex (CMMC) is a neurally mediated, cyclical contractile event that propagates down the large bowel, propelling faecal matter. Disruption of this event can lead to severe constipation. The nervous system mediating this event lies purely within the gut wall; it is referred to as the enteric nervous system or 'little brain'. We have used calcium imaging to measure the activity in different classes of enteric neurons (sensory, interneurons, and excitatory and inhibitory motor neurons) and the adjacent smooth muscle to determine how this important motor event is generated. Here it is shown that spontaneous serotonin release from the intestinal mucosa is necessary for activating a particular class of sensory neurons that leads to the initiation of CMMCs.

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Ozone activates airway nerves via the selective stimulation of TRPA1 ion channels (p 423-433)
Thomas E. Taylor-Clark, Bradley J. Undem
Published Online: Jan 29 2010 3:21AM
DOI: 10.1113/jphysiol.2009.183301

Non-technical summary
Inhalation of ozone is a major health risk in industrialized nations. Ozone induces respiratory symptoms, probably via the activation of neural pathways. However, the specifics of this interaction are unknown. Here we demonstrate that ozone directly activates a subset of sensory nerves in the mouse lung. Sensitivity to ozone correlated with a transient receptor potential (TRP) A1 agonist. Using dissociated neurones as an in vitro model of sensory nerves, we demonstrate that ozone activates a subset of neurones from wild-type mice, but not from TRPA1-deficient mice. Finally, expression of TRPA1 channels on a human cell line conferred ozone sensitivity. Thus ozone is not an indiscriminate neuronal activator, but rather it selectively activates airway nerves by directly stimulating TRPA1.

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Cones perform a non-linear transformation on natural stimuli (p 435-446)
D. Endeman, M. Kamermans
Published Online: Jan 29 2010 3:21AM
DOI: 10.1113/jphysiol.2009.179036

Non-technical summary
Natural images falling on the retina contain a large variety of intensities and contrasts. In order to prevent saturation of retinal neurons, the photoreceptors contain a mechanism that scales the intensities in the images such that saturation is prevented. In this study we investigated the underlying mechanism and found that this is a highly non-linear mechanism. It enhances the responses to small changes in intensity and it reduces the responses to high intensities. The comparison between direct measurements of light responses of cones in the goldfish retina and analysis of the behaviour of the biophysical model of vertebrate photoreceptors shows that the non-linear behaviour can fully be understood based on the known biochemical reactions in the cones.

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NMDAR-mediated EPSCs are maintained and accelerate in time course during maturation of mouse and rat auditory brainstem in vitro (p 447-463)
Joern R. Steinert, Michael Postlethwaite, Melissa D. Jordan, Tatyana Chernova, Susan W. Robinson, Ian D. Forsythe
Published Online: Jan 29 2010 3:21AM
DOI: 10.1113/jphysiol.2009.184317

Non-technical summary
Receptor-ion channel proteins called Glutamate Receptors are studied at one identified synaptic junction (calyx of Held) in the brainstem auditory pathway (concerning hearing). They detect the neurotransmitter glutamate at excitatory synapses and excite target neurons. The ubiquitous N-methyl-D-aspartate receptor (NMDAR) is a special glutamate receptor subclass involved in development, learning and memory; four subunits (including both NR1 and NR2 subtypes) must combine to make a functional channel. We show that as animals mature, NMDARs generate smaller and faster synaptic currents which are well coupled to nitric oxide signalling, and these channels are composed of NR1, NR2A and NR2C subunits. This knowledge is crucial to understand the diverse roles of NMDARs at different synapses and contributes to knowledge about development and aging.

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CARDIOVASCULAR

Sodium accumulation promotes diastolic dysfunction in end-stage heart failure following Serca2 knockout (p 465-478)
William E. Louch, Karina Hougen, Halvor K. Mørk, Fredrik Swift, Jan M. Aronsen, Ivar Sjaastad, Henrik M. Reims, Borghild Roald, Kristin B. Andersson, Geir Christensen, Ole M. Sejersted
Published Online: Jan 29 2010 3:21AM
DOI: 10.1113/jphysiol.2009.183517

Non-technical summary
In heart failure, both contraction and relaxation of the heart become impaired, which decreases the ability of the heart to pump blood. These changes result, at least in part, from altered calcium homeostasis in individual cardiac muscle cells. We show that loss of a calcium pump which recycles calcium into stores leads to heart failure development, involving deficient contraction and relaxation. However, accumulation of sodium additionally impairs relaxation by inhibiting calcium removal from the cell. These results suggest that heart failure may be treated by improving both calcium and sodium homeostasis in muscle cells.

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SKELETAL MUSCLE AND EXERCISE

Temperature jump induced force generation in rabbit muscle fibres gets faster with shortening and shows a biphasic dependence on velocity (p 479-493)
K. W. Ranatunga, H. Roots, G. W. Offer
Published Online: Jan 29 2010 3:21AM
DOI: 10.1113/jphysiol.2009.179200

Non-technical summary
In experiments on fully activated single muscle fibres at ∼10°C, we examined the active force when the muscle fibre was shortening at different velocities and when its temperature was rapidly increased by a laser pulse. The laser pulse induced a temperature jump of 3-4°C in the fibre in 0.2 milliseconds, or 1/5000th of a second. A temperature jump induced a rise in force both in isometric muscle fibre (no shortening) and in steadily shortening muscle fibres. The speed of the temperature-jump-induced force rise and its relative amplitude increased markedly as the shortening velocity was increased. Our results show that mechanism of force generation in active muscle is such that it is both temperature sensitive and enhanced by shortening.

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The mechanism of the resistance to stretch of isometrically contracting single muscle fibres (p 495-510)
Luca Fusi, Massimo Reconditi, Marco Linari, Elisabetta Brunello, Ravikrishnan Elangovan, Vincenzo Lombardi, Gabriella Piazzesi
Published Online: Jan 29 2010 3:21AM
DOI: 10.1113/jphysiol.2009.178137

Non-technical summary
In skeletal muscle the motor protein myosin II has two identical heads, of which only one at a time interacts with actin during isometric contraction or shortening. Based on X-ray diffraction, the dimeric structure of this molecular motor has been recently associated to the braking action of muscle upon stretch. In this work, submillisecond stiffness changes in the muscle sarcomere give the evidence that stretch induced distortion of the actin-attached motor domain of the myosin dimers away from the centre of the sarcomere provides the steric conditions for rapid attachment of the second motor domain. New motors attach at about 7.5 × 10⁴ s⁻¹ explaining the efficient increase of the resistance of active muscle to sudden increase in load.

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Dihydrotestosterone activates the MAPK pathway and modulates maximum isometric force through the EGF receptor in isolated intact mouse skeletal muscle fibres (p 511-525)
M. M. Hamdi, G. Mutungi
Published Online: Jan 29 2010 3:21AM
DOI: 10.1113/jphysiol.2009.182162

Non-technical summary
Anabolic-androgenic steroids are derivatives of the male sex hormone testosterone widely prescribed for the treatment of muscle wasting in conditions such as old age, cancer, chronic renal failure and HIV-AIDS. In this study, we examined the effects of one of these derivatives, dihydrotestosterone (DHT), in mouse skeletal muscle cells. Our results show that DHT can increase force in fast twitch muscle cells and decrease it in slow twitch cells within a few minutes of application. In contrast, testosterone did not affect force production in either cell type. From these findings, we suggest that DHT is the more potent hormone in mammalian skeletal muscle cells and that it may be more beneficial than testosterone in the treatment of muscle wasting.

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INTEGRATIVE

Adaptations in placental phenotype support fetal growth during undernutrition of pregnant mice (p 527-538)
P. M. Coan, O. R. Vaughan, Y. Sekita, S. L. Finn, G. J. Burton, M. Constancia, A. L. Fowden
Published Online: Jan 29 2010 3:21AM
DOI: 10.1113/jphysiol.2009.181214

Non-technical summary
Undernutrition during pregnancy reduces birth weight and programmes adulthood disease, but its effects on the placenta, responsible for supplying nutrients for fetal growth, remain largely unknown. This study shows that placentas from undernourished mice are small, but transport more nutrients from mother to fetus per gram. This happens, partly, by changes in the placental transport surface and gene expression for specific nutrient transporters. Undernourished placentas express less of the growth stimulator Igf2, but this is not due to altered DNA methylation. The placenta, therefore, adapts to help the fetus grow when its own growth is compromised by maternal undernutrition. Consequently, the placenta's response to the environment may be an important factor determining the risk of adult disease programmed before birth.

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Influence of high altitude on cerebrovascular and ventilatory responsiveness to CO₂ (p 539-549)
Jui-Lin Fan, Keith R. Burgess, Riche Basnyat, Kate N. Thomas, Karen C. Peebles, Samuel J. E. Lucas, Rebekah A. I. Lucas, Joseph Donnelly, James D. Cotter, Philip N. Ainslie
Published Online: Jan 29 2010 3:21AM
DOI: 10.1113/jphysiol.2009.184051

Non-technical summary
Upon ascent to high altitude, breathing increases to help maintain oxygen levels in the body. Changes in breathing affect the acid–base balance in the blood. Both of these factors can influence brain blood flow which, in turn, can influence breathing. In the current study, we examined the complex relationships between breathing and brain blood flow in 17 healthy volunteers at sea level and following a 9 day trek to 5050 m, near Everest base camp. Our findings provide new insight into how the control of brain blood flow and breathing are altered at high altitude and how they are regulated by the acid–base status of the blood. Understanding these complex mechanisms is relevant to many pathological conditions associated with reduced oxygen levels.

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