A unique alkaline pH-regulated and fatty acid-activated tandem pore domain potassium channel (K2P) from a marine sponge.

A cDNA encoding a potassium channel of the two-pore domain family (K(2P), KCNK) of leak channels was cloned from the marine sponge Amphimedon queenslandica. Phylogenetic analysis indicated that AquK(2P) cannot be placed into any of the established functional groups of mammalian K(2P) channels. We used the Xenopus oocyte expression system, a two-electrode voltage clamp and inside-out patch clamp electrophysiology to determine the physiological properties of AquK(2P). In whole cells, non-inactivating, voltage-independent, outwardly rectifying K(+) currents were generated by external application of micromolar concentrations of arachidonic acid (AA; EC(50) ∼30 µmol l(-1)), when applied in an alkaline solution (≥pH 8.0). Prior activation of channels facilitated the pH-regulated, AA-dependent activation of AquK(2P) but external pH changes alone did not activate the channels. Unlike certain mammalian fatty-acid-activated K(2P) channels, the sponge K(2P) channel was not activated by temperature and was insensitive to osmotically induced membrane distortion. In inside-out patch recordings, alkalinization of the internal pH (pK(a) 8.18) activated the AquK(2P) channels independently of AA and also facilitated activation by internally applied AA. The gating of the sponge K(2P) channel suggests that voltage-independent outward rectification and sensitivity to pH and AA are ancient and fundamental properties of animal K(2P) channels. In addition, the membrane potential of some poriferan cells may be dynamically regulated by pH and AA.

Non-invasive MR imaging techniques for measuring femoral arterial flow in a pediatric and adolescent cohort.

Magnetic Resonance Imaging (MRI) is well-suited for imaging peripheral blood flow due to its non-invasive nature and excellent spatial resolution. Although MRI is routinely used in adults to assess physiological changes in chronic diseases, there are currently no MRI-based data quantifying arterial flow in pediatric or adolescent populations during exercise. Therefore the current research sought to document femoral arterial blood flow at rest and following exercise in a pediatric-adolescent population using phase contrast MRI, and to present test-retest reliability data for this method. Ten healthy children and adolescents (4 male; mean age 14.8 ± 2.4 years) completed bloodwork and resting and exercise MRI. Baseline images consisted of PC-MRI of the femoral artery at rest and following a 5 × 30 s of in-magnet exercise. To evaluate test-retest reliability, five participants returned for repeat testing. All participants successfully completed exercise testing in the MRI. Baseline flow demonstrated excellent reliability (ICC = 0.93, p = 0.006), and peak exercise and delta rest-peak flow demonstrated good reliability (peak exercise ICC = 0.89, p = 0.002, delta rest-peak ICC = 0.87, p = 0.003) between-visits. All three flow measurements demonstrated excellent reliability when assessed with coefficients of variance (CV's) (rest: CV = 6.2%; peak exercise: CV = 7.3%; delta rest-peak: CV = 7.1%). The mean bias was small for femoral arterial flow. There was no significant mean bias between femoral artery flow visits 1 and 2 at peak exercise. There were no correlations between age or height and any of the flow measurements. There were no significant differences between male and female participants for any of the flow measurements. The current study determined that peripheral arterial blood flow in children and adolescents can be evaluated using non-invasive phase contrast MRI. The MRI-based techniques that were used in the current study for measuring arterial flow in pediatric and adolescent patients demonstrated acceptable test-retest reliability both at rest and immediately post-exercise.

The ventilatory response to sine wave variation in exercise loads and limb movement frequency.

The current study's experiments tested the hypothesis that limb movement frequency is a significant determinant of exercise hyperpnoea. To this end, 19 healthy participants walked on a treadmill, where work was varied sinusiodally by alterations in either treadmill speed or grade. Measured responses were fitted with sine waves to determine their amplitudes and phase angles. Walking pace amplitude was greater during speed tests than grade tests, and phase lag relative to the treadmill smaller, as expected. Ventilation, carbon dioxide production, and oxygen uptake amplitudes were higher during speed tests than grade tests. Further, phase angle lags relative to the treadmill for these measures were shorter during speed tests than grade tests. We concluded that these findings demonstrate the presence of changes in breathing during exercise that can be attributed to changes in limb movement frequency.

Limb movement frequency is a significant modulator of the ventilatory response during submaximal cycling exercise in humans.

Human experimentation investigating the contribution of limb movement frequency in determining the fast exercise drive to breathe has produced controversial findings. To evaluate the role of limb movement frequency in determining the fast exercise drive to breathe, endurance runners and recreationally-active controls performed two sinusoidal exercise protocols on a cycle ergometer. One protocol was performed at constant workload with sinusoidal pedaling cadence, and a second with sinusoidal workload at constant cadence. Metabolic rate (VO2) increases and means were matched between these two experiments. The ventilatory response was significantly faster when limb movement speed was varied, compared to when pedal loading was varied (18.49 ± 15.6s vs. 50.5 ± 14.5s, p<0.05). Ventilation response amplitudes were significantly higher during pedal cadence variation versus pedal loading variation (3.99 ± 0.25 vs. 2.58 ± 0.17 L/min, p<0.05). Similar findings were obtained for endurance athletes, with significantly attenuated ventilation responses to exercise versus control subjects. We conclude that fast changes in limb movement frequency are a potent stimulus for ventilation at submaximal workloads, and that this response is susceptible to attenuation through training.

Effects of concurrent inspiratory and expiratory muscle training on respiratory and exercise performance in competitive swimmers.

The efficiency of the respiratory system presents significant limitations on the body's ability to perform exercise due to the effects of the increased work of breathing, respiratory muscle fatigue, and dyspnoea. Respiratory muscle training is an intervention that may be able to address these limitations, but the impact of respiratory muscle training on exercise performance remains controversial. Therefore, in this study we evaluated the effects of a 12-week (10 sessions week(-1)) concurrent inspiratory and expiratory muscle training (CRMT) program in 34 adolescent competitive swimmers. The CRMT program consisted of 6 weeks during which the experimental group (E, n = 17) performed CRMT and the sham group (S, n = 17) performed sham CRMT, followed by 6 weeks when the E and S groups performed CRMT of differing intensities. CRMT training resulted in a significant improvement in forced inspiratory volume in 1 s (FIV1.0) (P = 0.050) and forced expiratory volume in 1 s (FEV1.0) (P = 0.045) in the E group, which exceeded the S group's results. Significant improvements in pulmonary function, breathing power, and chemoreflex ventilation threshold were observed in both groups, and there was a trend toward an improvement in swimming critical speed after 12 weeks of training (P = 0.08). We concluded that although swim training results in attenuation of the ventilatory response to hypercapnia and in improvements in pulmonary function and sustainable breathing power, supplemental respiratory muscle training has no additional effect except on dynamic pulmonary function variables.