New Insights in the Contribution of Voltage-Gated Nav Channels to Rat Aorta Contraction

BACKGROUND: Despite increasing evidence for the presence of voltage-gated Na(+) channels (Na(v)) isoforms and measurements of Na(v) channel currents with the patch-clamp technique in arterial myocytes, no information is available to date as to whether or not Na(v) channels play a functional role in arteries. The aim of the present work was to look for a physiological role of Na(v) channels in the control of rat aortic contraction. METHODOLOGY/PRINCIPAL FINDINGS: Na(v) channels were detected in the aortic media by Western blot analysis and double immunofluorescence labeling for Na(v) channels and smooth muscle alpha-actin using specific antibodies. In parallel, using real time RT-PCR, we identified three Na(v) transcripts: Na(v)1.2, Na(v)1.3, and Na(v)1.5. Only the Na(v)1.2 isoform was found in the intact media and in freshly isolated myocytes excluding contamination by other cell types. Using the specific Na(v) channel agonist veratridine and antagonist tetrodotoxin (TTX), we unmasked a contribution of these channels in the response to the depolarizing agent KCl on rat aortic isometric tension recorded from endothelium-denuded aortic rings. Experimental conditions excluded a contribution of Na(v) channels from the perivascular sympathetic nerve terminals. Addition of low concentrations of KCl (2-10 mM), which induced moderate membrane depolarization (e.g., from -55.9+/-1.4 mV to -45.9+/-1.2 mV at 10 mmol/L as measured with microelectrodes), triggered a contraction potentiated by veratridine (100 microM) and blocked by TTX (1 microM). KB-R7943, an inhibitor of the reverse mode of the Na(+)/Ca(2+) exchanger, mimicked the effect of TTX and had no additive effect in presence of TTX. CONCLUSIONS/SIGNIFICANCE: These results define a new role for Na(v) channels in arterial physiology, and suggest that the TTX-sensitive Na(v)1.2 isoform, together with the Na(+)/Ca(2+) exchanger, contributes to the contractile response of aortic myocytes at physiological range of membrane depolarization

Ih Current Is Necessary to Maintain Normal Dopamine Fluctuations and Sleep Consolidation in Drosophila

HCN channels are becoming pharmacological targets mainly in cardiac diseases. But apart from their well-known role in heart pacemaking, these channels are widely expressed in the nervous system where they contribute to the neuron firing pattern. Consequently, abolishing Ih current might have detrimental consequences in a big repertoire of behavioral traits. Several studies in mammals have identified the Ih current as an important determinant of the firing activity of dopaminergic neurons, and recent evidences link alterations in this current to various dopamine-related disorders. We used the model organism Drosophila melanogaster to investigate how lack of Ih current affects dopamine levels and the behavioral consequences in the sleep∶activity pattern. Unlike mammals, in Drosophila there is only one gene encoding HCN channels. We generated a deficiency of the DmIh core gene region and measured, by HPLC, levels of dopamine. Our data demonstrate daily variations of dopamine in wild-type fly heads. Lack of Ih current dramatically alters dopamine pattern, but different mechanisms seem to operate during light and dark conditions. Behaviorally, DmIh mutant flies display alterations in the rest∶activity pattern, and altered circadian rhythms. Our data strongly suggest that Ih current is necessary to prevent dopamine overproduction at dark, while light input allows cycling of dopamine in an Ih current dependent manner. Moreover, lack of Ih current results in behavioral defects that are consistent with altered dopamine levels

A New Course using CAT/CAL for the Teaching of Rotating Machines

This paper presents the backgrounds and the contents of a new course for the teaching of rotating machines based on this philosophy

Which Foetal-Pelvic Variables Are Useful for Predicting Caesarean Section and Instrumental Assistance

International audiencea narrow pelvic inlet had a greater risk for requiring CD. The most efficient variables for discrimination were the transverse diameter and foetal weight. The antero-posterior inlet and obstetric conjugate were considered in this model, with the former being a useful variable but not the latter. For the SVD versus IAD model, the most important variables were the foetal variables, particularly the bi-parietal diameter. Women with a reduced antero-posterior outlet diameter and a narrow pubic arch were more at risk of requiring an IAD. Conclusion: The antero-posterior inlet was an efficient variable unlike the obstetric conjugate. The obstetric conjugate diameter should no longer be considered a useful variable in estimating the arrest of labour. Antero-posterior inlet diameter was a sagittal variable that should be taken into account. The comparison of sub-pubic angle and bi-parietal and antero-posterior outlet diameters was useful in identifying a risk of requiring instrumental assistance. Abstract Objective: To assess the variables useful to predict caesare-an delivery (CD) and instrumental assistance, through the analysis of a large number of foetal-pelvic variables, using discriminant analysis. Materials and Methods: One hundred and fourteen pregnant women were included in this single-centre prospective study. For each mother-foetus pair, 43 pelvic and 18 foetal variables were measured. Partial least squares-discriminant analysis was performed to identify foe-tal-pelvic variables that could statistically separate the 3 delivery modality groups: spontaneous vaginal delivery (SVD), CD, and instrument-assisted delivery (IAD). Results: For the SVD versus CD model, voluminous foetuses and women wit