Interplay between hypoactivity, muscle properties and motor command: How to escape the vicious deconditioning circle?

Activity-dependent processes addressing the central nervous system (CNS) and musculoskeletal structures are critical for maintaining motor performance. Chronic reduction in activity, whether due to a sedentary lifestyle or extended bed rest, results in impaired performance in motor tasks and thus decreased quality of life. In the first part of this paper, we give a narrative review of the effects of hypoactivity on the neuromuscular system and behavioral outcomes.

A functional tandem between transient receptor potential canonical channels 6 and calcium-dependent chloride channels in human epithelial cells.

TRPC6 plays important human physiological functions, notably in artery and arterioles constriction, in regulation of vascular volume and in bronchial muscle constriction. It is implicated in pulmonary hypertension, cardiovascular disease, and focal segmental glomerulosclerosis and seems to play a role in cancer development. Previously, we identified Guanabenz, an α2-adrenergic agonist used for hypertension treatment (Wytensin®), as an activator of calcium-dependent chloride channels (CaCC) in human Cystic Fibrosis (CF) nasal epithelial cells by transiently increasing [Ca2+]i via an influx of extracellular Ca2+.

Effect of nitric oxide on epithelial ion transports in noncystic fibrosis and cystic fibrosis human proximal and distal airways.

The airways of patients with cystic fibrosis (CF) exhibit decreased nitric oxide (NO) concentrations, which might affect airway function. The aim of this study was to determine the effects of NO on ion transport in human airway epithelia. Primary cultures of non-CF and CF bronchial and bronchiolar epithelial cells were exposed to the NO donor sodium nitroprusside (SNP), and bioelectric variables were measured in Ussing chambers.

Stimulation of Wild-Type, F508del- and G551D-CFTR Chloride Channels by Non-Toxic Modified pyrrolo[2,3-b]pyrazine Derivatives.

Cystic fibrosis (CF) is a major inherited disorder involving abnormalities of fluid and electrolyte transport in a number of different organs due to abnormal function of cystic fibrosis transmembrane conductance regulator (CFTR) protein. We recently identified a family of CFTR activators, which contains the hit: RP107 [7-n-butyl-6-(4-hydroxyphenyl)[5H]-pyrrolo[2,3-b]pyrazine]. Here, we further evaluated the effect of the chemical modifications of the RP107-OH radical on CFTR activation.

Transient receptor potential canonical channel 6 links Ca2+ mishandling to cystic fibrosis transmembrane conductance regulator channel dysfunction in cystic fibrosis.

In cystic fibrosis (CF), abnormal control of cellular Ca(2+) homeostasis is observed. We hypothesized that transient receptor potential canonical (TRPC) channels could be a link between the abnormal Ca(2+) concentrations in CF cells and cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. We measured the TRPC and CFTR activities (using patch clamp and fluorescent probes) and interactions (using Western blotting and co-immunoprecipitation) in CF and non-CF human epithelial cells treated with specific and scrambled small interfering RNA (siRNA).

Acute respiratory failure involving an R variant of Mycobacterium abscessus.

We report the case of a cystic fibrosis patient colonized with a smooth-morphotype form of Mycobacterium abscessus who developed acute respiratory failure with the emergence of an isogenic rough (R) variant while he was recovering from peritonitis-induced shock. This report emphasizes the role of R forms in severe M. abscessus infections.

Functional properties of mixed cystic fibrosis and normal bronchial epithelial cell cultures.

Cystic fibrosis (CF) airway epithelia exhibit altered Cl(-) and Na(+) transport properties and increased IL-8 secretion. In the present study, we examined whether a small proportion of cells with a normal phenotype could normalize the ion transport and IL-8 secretion properties of a CF airway epithelial cell layer. We obtained three types of primary cultures of human bronchial epithelial cells: one composed of 100% non-CF cells, one of 100% CF cells, and one of 10% non-CF and 90% CF cells ("cocultures").

Guanabenz, an alpha2-selective adrenergic agonist, activates Ca2+-dependent chloride currents in cystic fibrosis human airway epithelial cells.

In cystic fibrosis respiratory epithelial cells, the absence or dysfunction of the chloride channel CFTR (Cystic Fibrosis Transmembrane conductance Regulator) results in reduced chloride ion transport. In contrast, Ca2+-stimulated Cl- secretion is intact in cystic fibrosis airway epithelia. One possible target for drug discovery aiming at treating cystic fibrosis is to correct the ionic imbalance through stimulation of alternative ionic pathways that may compensate the failure of epithelial Cl- conductance.

Expression of cystic fibrosis transmembrane conductance regulator in the human distal lung.

The determination of the expression of cystic fibrosis transmembrane conductance regulator (CFTR) in the lung is essential for a full understanding of the normal lung physiology and the pathogenesis of the lung disease in cystic fibrosis (CF). However, studies on the expression of CFTR in the distal adult human lung have yielded conflicting results despite functional evidence of expression of CFTR in bronchiolar and alveolar epithelial cells. We used 2 high-affinity monoclonal anti-CFTR antibodies, MAb24-1 and MAb13-1, to determine the expression of CFTR in samples of bronchiolar and alveolar tissues obtained from the same non-CF individuals.

Stimulation of salivary secretion in vivo by CFTR potentiators in Cftr+/+ and Cftr-/- mice.

Background: Physiologically, salivary secretion is controlled by cholinergic and adrenergic pathways but the role of ionic channels in this process is not yet clearly understood. In cystic fibrosis (CF), most exocrine glands failed to response to beta-adrenergic agonists.

Methods: To determine the implication of CFTR in this process, we measured in vivo the salivary secretion of Cftr(+/+) and Cftr(-/-) mice in the presence of 2 water-soluble benzo[c]quinolizinium derivatives; MPB-07 a potentiator of CFTR Cl(-) channel and MPB-05 an inactive analogue.

Ion and fluid transport properties of small airways in cystic fibrosis.

Rationale: Small airways constitute a major site of pathology in cystic fibrosis (CF) and provide most of the surface area of the conducting airways of the lung. Little is known, however, about the impact of CF on ion and fluid transport in small (bronchiolar) airways.

Objectives: To describe the ion and fluid transport properties of CF bronchiolar epithelium.