Experimental Physiology最新文献

Established methods of measuring functional residual capacity (FRC) involve sophisticated equipment and elaborate procedures. Here we present a new method based on CO₂ rebreathing that has a simple fast procedure and only requires end-tidal CO₂ monitoring. Ten healthy subjects with diverse anthropometric and respiratory parameters were studied in the sitting position. Reference FRC (RefFRC) and tidal volume (TV) were measured with a Cosmed Quark PFT/DLCO unit using the single-breath methane dilution technique in combination with spirometry. Rebreathing through an external dead space of precisely known volume and recording the rising end-tidal CO₂ value of the first two breaths allows the determination of effective lung volume (ELV) and the calculation of FRC. Two sets of measurements were made on each subject 15 min apart. Bland-Altman analysis of a comparison between FRC and RefFRC showed a mean bias of 0.04 L, with limits of agreement (LoA, 95% CI) of -1.24 to +1.32 L and a percentage error (PE) of 0.54. When the mean value of two observations from a subject (meanFRC) was compared to RefFRC we obtained a mean bias of -0.08 L, LoA (95% CI) of -0.88 to +0.72 L and PE of 0.23. The FRC data obtained demonstrate good absolute accuracy. An average of repeated measurements improves precision indicating that a criterion for exchangeability with the reference method can be met. The simplicity of the equipment and the procedure could make this method attractive in the pre-operative and the post-operative settings, as well as in out-of-hospital applications.

The principal processes that govern interstitial K⁺ ([K⁺]_o) buffering in mouse optic nerve (MON), a central white matter tract, either directly consume energy (Na⁺-K⁺-ATPase) or use transmembrane ion gradients created by energy-dependent pumps to enable the K⁺ fluxes that maintain a stable [K⁺]_o, and thus ready availability of utilisable energy substrate is vital in supporting MON function. We switched the artificial cerebrospinal fluid (aCSF) bathing isolated ex vivo MON from a glucose and physiological [K⁺] (3 mM) formulation to one in which glucose was replaced by lactate and [K⁺] was increased to supra-physiological concentrations ('stress aCSF'), to test the ability of an oxidative fuel to support astrocyte function when faced with the buffering-related increased energy demand that accompanies elevating [K⁺]_o. We recorded simultaneously the compound action potential (CAP) and [K⁺]_o with suction electrodes and ion-sensitive microelectrodes, respectively. Increases in aCSF [K⁺] were not matched by equivalent increases in [K⁺]_o, evidence of powerful buffering. The stress aCSF caused unexpected reciprocal CAP and [K⁺]_o oscillations and exhaustion of astrocyte energy reserves coupled with elevation of [K⁺]_o sufficient to activate axonal Na⁺ channels, the key factors required for their initiation. The oscillation profile was of a rise in [K⁺]_o towards aCSF [K⁺], followed by a restoration of [K⁺]_o towards baseline, driven by intermittent activation of the axonal Na⁺-K⁺-ATPase, a cyclical process that continued for several hours. These oscillations exposed the contrasting utility of lactate, supporting axonal CAPs and axonal dominance of buffering during the oscillations, but incapable of fuelling astrocyte function.

The aim of the study was to identify central determinants of ${\dot{V}}_{O_2\mathrm{peak}}$ using a 3-year longitudinal evaluation of left ventricular (LV) morphological and functional (global, tissue-Doppler and strain) outcome measures obtained at rest and during both submaximal and maximal exercise in a group of highly trained male youth soccer players (SP) and recreationally active male participants (CON). Once a year for 3 years, measurements were obtained in both the SP and CON groups (12.0 ± 0.3 and 11.7 ± 0.2 years of age, respectively, at the onset of the study). Cardiac ultrasound measures were used to identify LV morphological indices at rest and functional parameters during submaximal and maximal exercise. Training status (P < 0.0001) emerged as the only significant independent predictor of ${\dot{V}}_{O_2\mathrm{peak}}$ , when considering LV morphological variables. At maximal exercise, early diastolic filling (E) was a significant (P = 0.001) predictor of ${\dot{V}}_{O_2\mathrm{peak}}$ , irrespective of the influence of training status. Training status emerged as the significant predictor of ${\dot{V}}_{O_2\mathrm{peak}}$ across all models that were developed in this study. Minimal LV structural and functional adaptations at both rest and exercise influence ${\dot{V}}_{O_2\mathrm{peak}}$ , beyond the impact of training status alone. The broader implication of these findings is that the influence of LV cardiac adaptations on ${\dot{V}}_{O_2\mathrm{peak}}$ over time is mediated by the stimulus of training; this association occurs independently from the impact of growth and maturation on ${\dot{V}}_{O_2\mathrm{peak}}$ .

Extensive research in humans, dogs, rabbits, rats, mice and other mammals has consistently demonstrated that coronary blood flow (CBF) peaks during ventricular diastole. For example, studies using transthoracic Doppler echocardiography in anaesthetized rats and mice, isolated blood-perfused rat hearts and Doppler probes sutured to the myocardial surface have reported diastolic-dominant CBF. In contrast, while evaluating the effects of dietary salt on coronary vascular resistance in rats, we unexpectedly observed that left CBF peaked during ventricular systole. This observation prompted two follow-up protocols to test the hypothesis that left coronary flow in rats and mice peaks during systole. In Protocol 1, chronically instrumented conscious male Sprague-Dawley rats were implanted with telemetry pressure sensors and pulsed Doppler flow probes around the ascending aorta and left main coronary artery. Coronary and aortic flow waveforms exhibited nearly identical timing, indicating that CBF peaked during systole. In Protocol 2, anaesthetized, open-chest, mechanically ventilated rats and mice (both sexes) were studied. Doppler probes and ECG electrodes were used to compare the time from the R wave to the peak of both aortic and coronary flow. Student's paired t-test showed no significant difference between the two, confirming that coronary and aortic flow occur synchronously during systole. These findings demonstrate that, in rats and mice, left coronary blood flow peaks during ventricular systole - not diastole - challenging the widely accepted paradigm. This may reflect structural and haemodynamic features unique to small mammals, such as low ventricular wall tension and high heart rates.

The neurodevelopmental disorder fragile X syndrome (FXS) results from hypermethylation of the FMR1 gene, which prevents production of the FMRP protein. FMRP modulates the expression and function of a variety of proteins, including voltage-gated ion channels, such as hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels, which are integral to rhythmic activity in thalamic structures. Thalamocortical pathology, particularly involving the mediodorsal thalamus (MD), has been implicated in neurodevelopmental disorders such as FXS. MD connectivity with the medial prefrontal cortex (mPFC) is integral to executive functions such as working memory and social behaviours that are disrupted in FXS. We used a combination of retrograde labelling and ex vivo brain slice whole-cell electrophysiology in 40 wild-type and 42 Fmr1 knockout male mice to investigate how a lack of Fmr1 affects intrinsic cellular properties in lateral (MD-L) and medial (MD-M) MD neurons that project to the mPFC (MD→mPFC neurons). In MD-L neurons, Fmr1 knockout decreased the HCN-mediated membrane properties voltage sag and membrane after-hyperpolarization. We also identified a delay in rebound spike timing in both complex bursts and low-threshold spikes. In Fmr1 knockout mice, reduced HCN channel activity in MD-L→mPFC neurons impaired both the timing and the magnitude of HCN-mediated membrane potential regulation. Changes in response timing might adversely affect rhythm propagation in Fmr1 KO thalamocortical circuitry. MD thalamic neurons are crucial for maintaining rhythmic activity involved in cognitive and affective functions. Understanding specific mechanisms of thalamocortical circuit activity might lead to therapeutic interventions for individuals with FXS and other conditions characterized by thalamic dysrhythmia.

It is widely held that in human, fibres of the corpus callosum mediate inter-hemispheric inhibition - deemed necessary to prevent a bilateral cerebrum from generating simultaneous and potentially conflicting outputs. Ostensible support comes from an electrophysiological phenomenon whereby the mean magnitude of 'test' motor evoked potentials (MEPs) obtained in response to magnetic stimuli delivered over the contralateral motor cortex is diminished when initial 'conditioning' magnetic stimuli have been applied 6-15 ms previously to the opposite motor cortex. A contrary view is that this phenomenon masks, rather than reveals, normal physiological processes. An alternative hypothesis is that cortical motor centres giving rise to efferent projections onto motoneurons innervating homologous muscles conduct reciprocal shaping of excitation. This hypothesis was examined in a large sample (205 participants) by correlating the amplitude of MEPs elicited by a conditioning stimulus (CS) with the amplitude of those elicited 10 ms later by a test stimulus (TS). The magnitudes of responses to the CS and TS were positively correlated. This remained the case following statistical compensation for an observed covariation of low amplitude fluctuations in the background (<2 µV root mean squared) electromyographic activity recorded in the (homologous) target muscles prior to stimulation. Although the coefficients representing the magnitude of association between responses to the CS and TS are small (rho < 0.20), they are reliable. These findings support the hypothesis that there is positive covariation in the excitability of corticospinal projections from the two cerebral hemispheres to homologous muscles of the upper limb.

Sustainable development is a growing global concern, but university students in scientific fields such as Physiology struggle to see its direct relevance to their studies. This research explores how an authentic assessment can integrate the United Nations (UN) sustainable development goals (SDGs) into Physiology education. Students were tasked to design and present a group poster on the connections between an SDG and Physiology. Through a mixed-methods approach utilizing questionnaires, pre- and post-assignment data were collected and the students' perceptions of the links and learning opportunities explored. Students reported a shift in how they perceived the intersection between Physiology and societal issues, with many expressing a newfound passion for sustainability. Awareness and understanding of the SDGs increased significantly (19% and 36%, respectively). Students made connections between Physiology and goals such as No Poverty (SDG1), Quality Education (SDG4), Gender Equality (SDG5), and Climate Action (SDG13). Thirteen of the 17 SDGs were rated as significantly more relevant to Physiology after the assignment, among these, several less obviously related goals like Affordable and Clean Energy (SDG7), Sustainable Cities and Communities (SDG11), Responsible Consumption and Production (SDG12), and Partnership for the Goals (SDG17). The remaining four (SDGs 2, 3, 6 and 15) had high initial relevance ratings, which did not significantly change, serving as an internal control supporting the validity of the observed increases for other goals. Responses to open questions suggested that the students' experience of the assessment was rich in context and meaning, making Physiology more than 'just being a uni topic'.