Journal of Physiology

An evolutionary heat shock response (HSR) protects most living species, including humans, from heat-induced macromolecular damage. However, its role in the pathogenesis of heat stroke is unknown. We examined the whole genome transcriptome in peripheral blood mononuclear cells of a cohort of subjects exposed to the same high environmental heat conditions, who developed heat stroke (n = 19) versus those who did not (n = 19). Patients with heat stroke had a mean rectal temperature at admission of 41.7±0.8°C, and eight were in deep coma (Glasgow Coma Score = 3)...

MicroRNAs are noncoding RNAs, approximately 22nt in length, which serve to negatively regulate gene expression through binding to complementary sequences in the 3'UTR of target mRNA. The microRNA-target interaction does not require perfect complementarity, meaning that an individual microRNA often has a pool of hundreds of gene targets. Equally, one 3'UTR can contain target sites for many different microRNAs. This gives rise to a complex web of molecular interactions. An emerging concept is that microRNAs have a role as 'master' regulators of certain cellular properties, simultaneously mediating the subtle repression of multiple related genes within a pathway or system, therefore achieving a common phenotypic output...

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We describe a novel application of methodology for high-density surface electromyography (HDsEMG) decomposition to identify motor unit (MU) firings in response to transcranial magnetic stimulation (TMS). The method is based on the MU filter estimation from HDsEMG decomposition with Convolution Kernel Compensation during voluntary isometric contractions and its application to contractions elicited by TMS. First, we simulated synthetic HDsEMG signals during voluntary contractions followed by simulated motor evoked potentials (MEPs) recruiting increasing proportion of the motor pool...

In neocortical layer-5 pyramidal neurons, the action potential (AP) is generated in the axon initial segment (AIS) when the membrane potential (Vm ) reaches the threshold for activation of the voltage-gated Na+ channels (VGNCs) Nav 1.2 and Nav 1.6. Yet, whereas it is known that these VGNCs differ in spatial distribution along the AIS and in biophysical properties, the understanding of the functional differences between the two channels remains elusive. Here, using ultrafast Na+ , Vm and Ca2+ imaging in combination with the partial block of Nav 1...

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Although hyperpolarization-activated cation (HCN) ion channels are well established to underlie cardiac pacemaker activity, their role in smooth muscle organs remains controversial. HCN-expressing cells are localized to renal pelvic smooth muscle (RPSM) pacemaker tissues of the murine upper urinary tract and HCN channel conductance is required for peristalsis. To date, however, the Ih pacemaker current conducted by HCN channels has never been detected in these cells, raising questions on the identity of RPSM pacemakers...

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Because of the biophysical relation between muscle fibre diameter and the propagation velocity of action potentials along the muscle fibres, motor unit conduction velocity could be a non-invasive index of muscle fibre size in humans. However, the relation between motor unit conduction velocity and fibre size has been only assessed indirectly in animal models and in human patients with invasive intramuscular EMG recordings, or it has been mathematically derived from computer simulations. By combining advanced non-invasive techniques to record motor unit activity in vivo, i...

Suppression of the extensor H-reflex by flexor afferent conditioning is thought to be produced by a long-lasting inhibition of extensor Ia-afferent terminals via GABAA receptor-activated primary afferent depolarization (PAD). Considering the recent finding that PAD does not produce presynaptic inhibition of Ia-afferent terminals, we examined in 28 participants if H-reflex suppression is instead mediated by post-activation depression of the extensor Ia-afferents triggered by PAD-evoked spikes and/or by a long-lasting inhibition of the extensor motoneurons...

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Sensory and corticospinal tract (CST) pathways activate spinal GABAergic interneurons that have axoaxonic connections onto proprioceptive (Ia) afferents that cause long-lasting depolarizations (termed primary afferent depolarization, PAD). In rodents sensory-evoked PAD is produced by GABAA receptors at nodes of Ranvier in Ia-afferents, rather than at presynaptic terminals, and facilitates spike propagation to motoneurons by preventing branch-point failures, rather than causing presynaptic inhibition. We examined in 40 human participants if putative activation of Ia-PAD by sensory or CST pathways can also facilitate Ia-afferent activation of motoneurons via the H-reflex...

This study investigated the role of diacylglycerol (DAG)-mediated protein kinase C (PKC) activation, ceramides accumulation, and inflammation in insulin-resistant female oxidative and glycolytic skeletal muscles induced by an obesogenic high-fat sucrose-enriched (HFS) diet. The HFS diet impaired insulin-stimulated AKTThr308 phosphorylation and glycogen synthesis, whereas rates of fatty acid oxidation and basal lactate production were significantly elevated in soleus (Sol), extensor digitorum longus (EDL), and epitrochlearis (Epit) muscles...

Skeletal muscle's isometric contractile properties are one of the classic structure-function relationships in all of biology allowing for extrapolation of single fibre mechanical properties to whole muscle properties based on the muscle's optimal fibre length and physiological cross-sectional area (PCSA). However, this relationship has only been validated in small animals and then extrapolated to human muscles which are much larger in terms of length and PCSA. The purpose of this study was to measure directly the in situ properties and function of the human gracilis muscle to validate this relationship...

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