Mutagenesis of the NaChBac sodium channel discloses a functional role for a conserved S6 asparagine

Asparagine is conserved in the S6 transmembrane segments of all voltage-gated sodium, calcium, and TRP channels identified to date. A broad spectrum of channelopathies including cardiac arrhythmias, epilepsy, muscle diseases, and pain disorders is associated with its mutation. To investigate its effects on sodium channel functional properties, we mutated the simple prokaryotic sodium channel NaChBac. Electrophysiological characterization of the N225D mutant reveals that this conservative substitution shifts the voltage-dependence of inactivation by 25 mV to more hyperpolarized potentials. The mutant also displays greater thermostability, as determined by synchrotron radiation circular dichroism spectroscopy studies of purified channels. Based on our analyses of high-resolution structures of NaChBac homologues, we suggest that the side-chain amine group of asparagine 225 forms one or more hydrogen bonds with different channel elements and that these interactions are important for normal channel function. The N225D mutation eliminates these hydrogen bonds and the structural consequences involve an enhanced channel inactivation

Morphological characterization of bushy cells and their inputs in the laboratory mouse (Mus musculus) anteroventral cochlear nucleus.

PMC3753269Spherical and globular bushy cells of the AVCN receive huge auditory nerve endings specialized for high fidelity neural transmission in response to acoustic events. Recent studies in mice and other rodent species suggest that the distinction between bushy cell subtypes is not always straightforward. We conducted a systematic investigation of mouse bushy cells along the rostral-caudal axis in an effort to understand the morphological variation that gives rise to reported response properties in mice. We combined quantitative light and electron microscopy to investigate variations in cell morphology, immunostaining, and the distribution of primary and non-primary synaptic inputs along the rostral-caudal axis. Overall, large regional differences in bushy cell characteristics were not found; however, rostral bushy cells received a different complement of axosomatic input compared to caudal bushy cells. The percentage of primary auditory nerve terminals was larger in caudal AVCN, whereas non-primary excitatory and inhibitory inputs were more common in rostral AVCN. Other ultrastructural characteristics of primary auditory nerve inputs were similar across the rostral and caudal AVCN. Cross sectional area, postsynaptic density length and curvature, and mitochondrial volume fraction were similar for axosomatic auditory nerve terminals, although rostral auditory nerve terminals contained a greater concentration of synaptic vesicles near the postsynaptic densities. These data demonstrate regional differences in synaptic organization of inputs to mouse bushy cells rather than the morphological characteristic of the cells themselves.JH Libraries Open Access Fun

The effect of household poverty on tuberculosis

pSETTING: Households in Malawi, Mongolia, Myanmar, the Philippines, Rwanda, Tanzania, Viet Nam and Zambia.OBJECTIVE To assess the relationship between household socio-economic level, both relative and absolute, and individual tuberculosis (TB) disease.DesignWe analysed national TB prevalence surveys from eight countries individually and in pooled multicountry models. Socio-economic level (SEL) was measured in terms of both relative household position and absolute wealth. The outcome of interest was whether or not an individual had TB disease. Logistic regression models were used to control for putative risk factors for TB disease such as age, sex and previous treatment history.ResultsOverall, a strong and consistent association between household SEL and individual TB disease was not found. Significant results were found in four individual country models, with the lowest socio-economic quintile being associated with higher TB risk in Mongolia, Myanmar, Tanzania and Viet Nam.ConclusionsTB prevalence surveys are designed to assess prevalence of disease and, due to the small numbers of cases usually detected, may not be the most efficient means of investigating TB risk factors. Different designs are needed, including measuring the SEL of individuals in nested case-control studies within TB prevalence surveys or among TB patients seeking treatment in health care facilities