ABSTRACT
Sodium channel alpha subunit genes expressed in the human brain, SCN1A, SCN2A, SCN3A and SCN8A, are subject to alternative splicing of coding exons 5N and 5A. In this study we examined expression of alpha subunit mRNA and exon 5 splicing in the developing mouse brain. Expression levels of Scn1a, Scn2a and Scn8a mRNAs increase postnatally, whereas Scn3a mRNA expression levels decrease. Scn1a mRNA contains only exon 5A, due to the absence of exon 5N in the mouse Scn1a gene. At birth, Scn2a is the only sodium channel alpha subunit mRNA that contains higher or equal amounts of the 5N isoform compared to the 5A isoform in most brain regions. In contrast, the predominant isoform of Scn3a and Scn8a mRNAs in the newborn mouse brain is 5A. 5N/5A ratios for each of the three mRNAs vary across brain regions, with cortex >or= hippocampus>thalamus>cerebellum. In all brain regions and for all three alpha subunits, 5N/5A ratios gradually decrease with age, levelling at a value between 0.1 and 0.2. These findings suggest potential involvement of common factors in the alternative splicing of exon 5 for all three transcripts, and that expression of these factors varies between brain regions and changes during development. Differences in the strength of exon 5N and/or exon 5A splice sites in Scn2a pre-mRNA as compared to Scn1a and Scn8a may underlie the observed differences in 5N/5A ratios in the three alpha subunit mRNAs.
Subject(s)
Brain/growth & development , Brain/metabolism , Gene Expression Regulation, Developmental/physiology , Protein Subunits/genetics , RNA, Messenger/genetics , Sodium Channels/genetics , Alternative Splicing/genetics , Animals , Animals, Newborn , Brain/anatomy & histology , Exons/genetics , Male , Mice , Mice, Inbred C57BL , NAV1.1 Voltage-Gated Sodium Channel , NAV1.2 Voltage-Gated Sodium Channel , NAV1.6 Voltage-Gated Sodium Channel , Nerve Tissue Proteins/chemistry , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Protein Isoforms/chemistry , Protein Isoforms/genetics , Protein Isoforms/metabolism , Protein Subunits/chemistry , Protein Subunits/metabolism , RNA Splice Sites/genetics , RNA, Messenger/metabolism , Sodium Channels/chemistry , Sodium Channels/metabolismSubject(s)
Hair/metabolism , Lead/blood , Occupational Exposure , Adolescent , Adult , Hair/chemistry , Humans , Industry , Lead Poisoning/prevention & control , Malaysia , Male , Middle Aged , ShipsSubject(s)
Copper , Hair/chemistry , Lead/analysis , Lead/blood , Mining , Adult , Child , Environmental Pollutants/analysis , Environmental Pollutants/blood , Environmental Pollutants/pharmacokinetics , Female , Hair/metabolism , Humans , Lead/pharmacokinetics , Malaysia , MaleABSTRACT
The process of standardization of the use of electron paramagnetic resonance (EPR) spectrometry in the determination of Mn(II) species in aqueous solution by comparison with atomic absorption spectrometry (AAS) is discussed. It is shown that EPR signals obtained from standardized aqueous solutions of manganese(II) perchlorate and nitrate in the concentration range of 0.05-2 mg/l. do not vary significantly over the pH range 2.1-7.0. Study of the effect (on the manganese EPR signals) of the addition of inorganic ions commonly found in significant concentrations in natural waters, viz. chloride, sulphate and bicarbonate, has shown that such ions, at the levels reported to occur in surface fresh waters, will not complex manganese(II); however, evidence is obtained that humic acid/manganese complexes could be present in such waters. The EPR signals are not affected by ionic strengths of the levels found in fresh waters.
ABSTRACT
The extent of current knowledge regarding the speciation of manganese in freshwaters is delineated, and the analytical methods whereby such knowledge is obtained are discussed. Particular attention is paid in the review to the use of electron paramagnetic resonance spectroscopy.
