Differential activation of the human costal and crural diaphragm during voluntary and involuntary breaths.

The diaphragm is the primary muscle that generates the negative intrathoracic pressure to drive inspiratory airflow. The diaphragm consists of two parts, the costal and crural portions, with different roles during inspiration in animals, particularly when the stimulus to breathe is increased. In this study, the neural drive to the costal and crural portions of the diaphragm was assessed in nine healthy participants [8 male, aged 32 ± 13 yr (mean ± SD)]. Inspiratory electromyographic activity (EMG) was recorded from the costal diaphragm by using an intramuscular electrode and from the crural diaphragm with a multipair gastroesophageal catheter. Participants performed voluntary augmented breaths at 120%, 140%, and 160% of their tidal volume and also underwent progressive hypercapnia to induce involuntary breathing. Irrespective of the task, the increase in crural activity (normalized to quiet breathing) was only ~60% of the increase in costal activity (slope: 0.56 ± 0.30, P < 0.001). The onset and peak timing of EMG activity was similar for the costal and crural diaphragm during quiet breathing. Thus, when stimulated by either a voluntary or involuntary drive to breathe above tidal volume, the neural drive to the diaphragm was greater to the costal than to the crural portion.NEW & NOTEWORTHY Simultaneous electromyographic recordings from the human costal and crural diaphragm during voluntary augmented breathing and involuntary rebreathing show that the increase in inspiratory crural diaphragm activity was ~60% of the increase in costal diaphragm activity. However costal to crural diaphragm activation did not differ between the two tasks. The dissociation in the amplitude of activation of the costal and crural diaphragm becomes apparent only as the drive to breathe increases above tidal breathing.

Increased diaphragm motor unit discharge frequencies during quiet breathing in people with chronic tetraplegia.

KEY POINTS: Respiratory muscle strength is compromised in people with tetraplegia, which may be compensated for by an increase in neural drive to the diaphragm. We found that the discharge frequencies of diaphragm motor units are higher in people with chronic tetraplegia compared with able-bodied people during quiet breathing. Furthermore, we found that the area of single motor unit potentials was increased in people with tetraplegia. These results suggest an increased motoneurone output to the diaphragm and remodelling of diaphragm motor units to maintain ventilation in tetraplegia. ABSTRACT: People with tetraplegia have reduced inspiratory muscle strength, ∼40% of able-bodied individuals. Paralysed or partially paralysed respiratory muscles as a result of tetraplegia compromise lung function, increase the incidence of respiratory infections and can cause dyspnoea. We hypothesised that reduced inspiratory muscle strength in tetraplegia may increase neural drive to the inspiratory muscles to maintain ventilation. We recorded the discharge properties of single motor units from the diaphragm in participants with chronic tetraplegia (8 males, 42-78 years, C3-C6 injury, AIS A-C) and able-bodied control participants (6 males matched for age and body mass index). In each group, 117 and 166 single motor units, respectively, were discriminated from recordings in the costal diaphragm using a monopolar electrode. A linear mixed-effects model analysis showed higher peak discharge frequencies of motor units during quiet breathing in tetraplegia (17.8 ± 4.9 Hz; mean ± SD) compared with controls (12.4 ± 2.2 Hz) (P < 0.001). There were no differences in tidal volume, inspiratory time or mean air flow between groups. Motor unit potentials in tetraplegia, compared with controls, were larger in amplitude (1.1 ± 0.7 mV and 0.5 ± 0.3 mV, respectively, P = 0.007) and area (1.83 ± 1.49 µV ms and 0.69 ± 0.52 µV ms, respectively, P = 0.003). The findings indicate that diaphragm motor unit remodelling is likely to have occurred in people with chronic tetraplegia and that there is an increase in diaphragm motor unit discharge rates during quiet breathing. These neural changes ensure that ventilation is maintained in people with chronic tetraplegia.

Discharge properties of human diaphragm motor units with ageing.

KEY POINTS: Ageing is associated with changes in the respiratory system including in the lungs, rib cage and muscles. Neural drive to the diaphragm, the principal inspiratory muscle, has been reported to increase during quiet breathing with ageing. We demonstrated that low-threshold motor units of the human diaphragm recruited during quiet breathing have similar discharge frequencies across age groups and shorter discharge times in older age. With ageing, motor unit action potential area increased. We propose that there are minimal functionally significant changes in the discharge properties of diaphragm motor units with ageing despite remodelling of the motor unit in the periphery. ABSTRACT: There are changes in the skeletal, pulmonary and respiratory neuromuscular systems with healthy ageing. During eupnoea, one study has shown relatively higher crural diaphragm electromyographic activity (EMG) in healthy older adults (>51 years) than in younger adults, but these measures may be affected by the normalisation process used. A more direct method to assess neural drive involves the measurement of discharge properties of motor units. Here, to assess age-related changes in neural drive to the diaphragm during eupnoea, EMG was recorded from the costal diaphragm using a monopolar needle electrode in participants from three age groups (n ≥ 7 each): older (65-80 years); middle-aged (43-55 years) and young (23-26 years). In each group, 154, 174 and 110 single motor units were discriminated, respectively. A mixed-effects linear model showed no significant differences between age groups for onset (group mean range 9.5-10.2 Hz), peak (14.1-15.0 Hz) or offset (7.8-8.5 Hz) discharge frequencies during eupnoea. The motor unit recruitment was delayed in the older group (by ∼15% of inspiratory time; p = 0.02 cf. middle-aged group) and had an earlier offset time (by ∼15% of inspiratory time; p = 0.04 cf. young group). However, the onset of multiunit activity was similar across groups, consistent with no global increase in neural drive to the diaphragm with ageing. The area of diaphragm motor unit potentials was ∼40% larger in the middle-aged and older groups (P < 0.02), which indicates axonal sprouting and re-innervation of muscle fibres associated with ageing, even in middle-aged participants.

Rheological observation of glassy dynamics of dilute polymer solutions near the coil-stretch transition in elongational flows.

It has long been conjectured that the macroscopic dynamics of dilute polymer solutions may exhibit a glasslike slowdown caused by ergodicity breaking, in the vicinity of the coil-stretch transition in elongational flows. We report experimental observations using a filament stretching rheometer that confirm the existence of such glassy states. It is observed that different time-dependent elongational strain-rate profiles lead to a pronounced history dependence and aging effects within a narrow range of strain rates. The results have a direct bearing on the analysis and design of processes employing dilute polymer solutions, such as ink-jet printing, surface coating, and turbulent-drag reduction.

Hormonal regulation of tight junction closure in the mouse mammary epithelium during the transition from pregnancy to lactation.

Closure of the tight junctions of the mammary epithelium has been shown to accompany the onset of copious milk secretion or lactogenesis, stage 2, in both goats and humans. Here we use injection of [(14)C]sucrose and FITC-albumin (fluorescein isothiocyanate-albumin) into the mammary duct to follow the course of tight junction closure during lactogenesis in mice. To examine the hormonal changes responsible, we ovariectomized day 16 or 17 pregnant mice and found that closure followed ovariectomy with a mean delay of 13.6+/-1.5 (s.e.m. ) h. That progesterone withdrawal is the trigger for closure was shown by the finding that injection of progesterone within 4 h of ovariectomy delayed closure and that closure occurred after injection of the progesterone antagonist RU 486 in intact late pregnant mice. Endocrine ablation studies showed that low to moderate concentrations of corticosterone and either placental lactogen or prolactin are necessary for tight junction closure triggered by progesterone withdrawal. Thus the hormonal requirements for tight junction closure are similar to those shown by other investigators to promote lactogenesis, stage 2. Further, the tight temporal control of tight junction permeability suggests that ovariectomy of the late pregnant mouse may be a good model for molecular studies of the lactogenic switch.

Tight junction regulation in the mammary gland.

Tight junctions form a narrow, continuous seal that surrounds each endothelial and epithelial cell at the apical border, and act to regulate the movement of material through the paracellular pathway. In the mammary gland, the tight junctions of the alveolar epithelial cells are impermeable during lactation, and thus allow milk to be stored between nursing periods without leakage of milk components from the lumen. Nonetheless mammary epithelial tight junctions are dynamic and can be regulated by a number of stimuli. Tight junctions of the mammary gland from the pregnant animal are leaky, undergoing closure around parturition to become the impermeable tight junctions of the lactating animal. Milk stasis, high doses of oxytocin, and mastitis have been shown to increase tight junction permeability. In general changes in tight junction permeability in the mammary gland appear to be the results of a state change and not assembly and disassembly of tight junctions. Both local factors, such as intramammary pressure and TGF-beta, and systemic factors, such as prolactin, progesterone, and glucocorticoids, appear to play a role in the regulation of mammary tight junctions. Finally, the tight junction state appears to be closely linked to milk secretion. An increase in tight junction permeability is accompanied by decrease in the milk secretion rate, and conversely, a decrease in tight junction permeability is accompanied by an increase in the milk secretion rate.

Primary sensory neurons express a Shaker-like potassium channel gene.

Developmentally regulated action potentials are a hallmark of Rohon-Beard cells, a class of sensory neurons. In these neurons as well as other primary spinal neurons of Xenopus laevis, the functional differentiation of delayed-rectifier potassium current regulates the waveform of the action potential during the initial day of its appearance. Later, the acquisition of another voltage-dependent potassium current--the A current--plays a major role in regulating excitability. In order to understand the molecular basis of this functional differentiation, genes encoding voltage-dependent potassium currents expressed in the embryonic amphibian nervous system are being cloned. Here, we report the functional properties and developmental localization of a second Xenopus Shaker-like gene (Xenopus Kv 1.1; XSha1; GenBank accession number M94258) encoding a potassium current. Homology screening with the mouse gene MBK1 led to its isolation. Functional expression in oocytes identifies it as a delayed-rectifier current when assembled as a homooligomeric structure. Specific transcripts corresponding to XSha1 and to the previously cloned gene XSha2 are both detectable by RNase protection in RNA isolated from the embryonic nervous system. However, whole-mount in situ hybridization reveals the temporal pattern and cellular localization of XSha1 but not XSha2 mRNA, suggesting that the concentration of XSha2 transcripts in individual cells is lower than the threshold for detection by this method. Of particular interest, Rohon-Beard cells express XSha1 mRNA. In addition, XSha1 mRNA is detected in several structures containing neural crest derivatives including spinal ganglia, the trigeminal ganglion, and branchial arches; its presence in motor nerves and lateral spinal tracts suggests that both CNS and PNS glia express the mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Milrinone produces a positive inotropy but is not inhibitory to gastric ion transport.

The cardiac drugs ouabain and milrinone are positive inotropic agents. Since ouabain has inhibitory effects on ion transport in the gastrointestinal tract associated with vasoconstriction and hypoxia, milrinone needed to be tested also. This report indicates that therapeutic levels of milrinone on either side of the isolated stomach wall of the guinea pig has no significant effects on active chloride ion transport or the electrical parameters of the tissue. To verify that milrinone was active in the heart at these same levels, contractility of the isolated heart of the guinea pig was measured. Milrinone significantly increased ventricular pressure and pressure development. Thus milrinone may be expected to exert its inotropic stimulation of the heart during heart failure without compromising gastrointestinal functions.

Effects of bile salts and prostaglandins on sodium transport in isolated rat gastric mucosa.

To determine whether prostaglandins may protect against bile salt inhibition of ion transport in the stomach, gastric mucosal tissue was isolated from the rat and mounted in flux chambers. Transport of Na+ was traced with radioisotopes in the absence of bile salts and then in the presence of conjugated taurocholate or unconjugated deoxycholate at low, intermediate and high mucosal concentrations (1, 5 and 15 mmol/1). At a high (7.40) or low (3.4) mucosal pH, only the unconjugated deoxycholate inhibited active Na+ transport from mucosa to submucosa with respect to untreated controls. Inhibition of Na+ transport was apparent at a low level of deoxycholate, which also inhibited the electrical potential difference. Intermediate and high levels of deoxycholate lowered the tissue resistance. When the tissues were exposed to mucosal prostaglandin E2 or its 16,16-dimethyl analogue before and during acidified taurocholate administration, Na+ transport was not changed significantly but the electrical resistance remained high. Thus, unconjugated bile salt is more potent than conjugated bile salt in inhibiting Na+ transport and breaking the gastric mucosal barrier, and prostaglandins may afford some small protection.