Experimental physiology
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Experimental physiology · Jan 2014
ReviewStructure and function of voltage-gated sodium channels at atomic resolution.
Voltage-gated sodium channels initiate action potentials in nerve, muscle and other excitable cells. Early physiological studies described sodium selectivity, voltage-dependent activation and fast inactivation, and developed conceptual models for sodium channel function. ⋯ Structural models for voltage-dependent activation, sodium selectivity and conductance, drug block and both fast and slow inactivation are discussed. A perspective for the future envisions new advances in understanding the structural basis for sodium channel function and the opportunity for structure-based discovery of novel therapeutics.
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Experimental physiology · Jan 2014
The cardiovascular actions of fractalkine/CX3CL1 in the hypothalamic paraventricular nucleus are attenuated in rats with heart failure.
The paraventricular nucleus (PVN) of the hypothalamus plays an important role in the regulation of sympathetic nerve activity, which is significantly elevated in chronic heart failure (CHF). Fractalkine (FKN) and its cognate receptor, CX3CR1, are constitutively expressed in the central nervous system, but their role and physiological significance are not well known. The aims of the present study were to determine whether FKN plays a cardiovascular role within the PVN and to investigate how the actions of FKN might be altered in CHF. ⋯ We found a significant increase in CX3CR1 mRNA and protein expression, as determined by quantitative RT-PCR and Western blot analysis, respectively, in the PVN of rats with CHF compared with sham-operated control rats. We also found that the blood pressure effects of FKN (2.5 nmol in 50 nl) were significantly attenuated in rats with CHF (change in mean arterial pressure, -6 ± 3 mmHg) compared with sham-operated control rats (change in mean arterial pressure, -16 ± 6 mmHg). These data suggest that FKN and its receptor, CX3CR1, modulate cardiovascular function at the level of the PVN and that the actions of FKN within this nucleus are altered in heart failure.
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Experimental physiology · Jan 2014
Ontogeny and control of the heart rate power spectrum in the last third of gestation in fetal sheep.
Power spectral analysis of fetal heart rate variability has been proposed to provide a non-invasive estimate of autonomic balance. However, there are few systematic data before birth. We therefore examined developmental changes in the frequency power spectrum at very low (0-0.04 Hz), low (0.04-0.15 Hz) and high frequencies (0.15-0.4 Hz), as well as the ratio of low- to high-frequency power (LF/HF), in chronically catheterized, healthy fetal sheep at 0.6 (n = 8), 0.7 (n = 7) and 0.8 gestational age (ga; n = 11). ⋯ Consistent with this, although total spectral power was not significantly greater during HV sleep, there was a significant interaction between sleep state and frequency band (P = 0.02). Both atropine (P = 0.05) and 6-hydroxydopamine (P < 0.05) were associated with an overall reduction in spectral power but no significant effect on the LF/HF ratio. This study does not support substantial, consistent differences between the frequencies of sympathetic and parasympathetic activity in late-gestation fetal sheep.
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Experimental physiology · Dec 2013
Clinical TrialEffect of inspiratory muscle fatigue on exercise performance taking into account the fatigue-induced excess respiratory drive.
Inspiratory muscle fatigue (IMF) is suggested to compromise exercise performance, possibly via a respiratory muscle metaboreflex that impairs blood flow to working muscles, thereby accelerating the development of fatigue in these muscles. Cycling with IMF has also been associated with an excess ventilatory response, which could per se impair performance. Therefore, the present study investigated whether prior-induced IMF would affect subsequent cycling performance via increased quadriceps muscle fatigue alone and whether fatigue-induced excess ventilation would contribute to this impairment. ⋯ The reduction in P(tw) and Q(tw) was greater after PF-EX (P(tw), 17.3 ± 9.7%; Q(tw), 32.0 ± 10.8%) than after MATCH-ISO (P(tw), 10.8 ± 10.3%; Q(tw), 23.3 ± 15.2%; P < 0.05), which may explain the increased perception of exertion and earlier task failure with prior-induced IMF. The augmented ventilatory drive had no effect on reductions in P(tw) and Q(tw) after MATCH-ISO compared with C-ISO. Thus, prior-induced IMF reduces exercise performance, probably as a result of the increased quadriceps muscle fatigue and thus greater perception of exertion independent of the excess respiratory drive when cycling with fatigued inspiratory muscles.
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Experimental physiology · Oct 2013
Preload-adjusted left ventricular dP/dtmax: a sensitive, continuous, load-independent contractility index.
The classical indicators of left ventricular (LV) performances have been derived from pressure-volume (PV) and stroke work-volume plots obtained during various loading or pharmacological interventions. More recently, the preload-adjusted maximal change in pressure over time (PAdP/dtmax), derived from single beat PV analysis, has been shown to reflect the LV systolic performance accurately in varying conditions of inotropy and afterload. The objective of this study was to address whether PAdP/dtmax is a valid indicator of LV function in the setting of large preload variations, compared with the classical dP/dtmax-end-diastolic volume (EDV) and stroke work-EDV (preload recruitable stroke work) relationships. ⋯ In contrast, dP/dtmax-EDV increased significantly and exhibited a curvilinear response that was associated with a large inter- and intra-animal variability. In a model of acute preload reduction, PAdP/dtmax was found to be the best indicator of systolic LV function. Given its simplicity, this real-time index derived from single beat analysis should be tested further in clinical settings.