4-4-difluoro-4-bora-3a-4a-diaza-s-indacene and 1-4-dihydropyridine

A mitochondria-targetable probe Mito-DHP for nitric oxide (NO) was designed and synthesized by introducing dihydropyridine and triphenylphosphonium (TPP) moieties into boron dipyrromethene (BODIPY) dye. Mito-DHP was able to effectively detect nitric oxide through the aromatization of dihydropyridine to fluorescent pyridine product under oxygen-free conditions. The probe Mito-DHP showed high selectivity to NO over a number of reactive oxygen/nitrogen species (ROS/RNS) as well as high sensitivity (detection limit at 25nM), pH stability and bio-compatibility. Furthermore, Mito-DHP proved to target mitochondria specifically and to visualize both exogenous and endogenous NO in real time.

Topics: Animals; Boron Compounds; Cell Survival; Dihydropyridines; Fluorescent Dyes; Hep G2 Cells; Humans; Mice; Mitochondria; Nitric Oxide; Organophosphorus Compounds; RAW 264.7 Cells

Several factors have an influence on the improvement of muscle activity and motor co-ordination of mammals during post-natal development. One of them is voltage sensitive L-type calcium channel function. In striated muscles of adult mammals these channels are located in T-tubule membranes thus linking the on-coming action potential to the molecular process of muscle contraction. The postnatal development of L-type calcium channels is therefore critical not only for contraction but also for all subsequent motor learning. We used high affinity enantiomer of dihydropyridine labelled with a fluorophore in order to show the relative amount of L-type calcium channels by histofluorescence in tissue. We found by qualitative microscopical analysis that the amount of L-type calcium channels increased during the postnatal development in the mouse skeletal muscle (m. rectus femoris and m. gastrocnemius). We also noted variation between different fibre types in the increase of the amount of L-type calcium channels, as judged by the intensity of histofluorescence. We showed by histochemical staining and statistical analysis that the high density of L-type calcium channels in adult muscles is correlated with fast oxidative glycolytic fibre type of striated muscles rather than slow oxidative or fast glycolytic fibres. Based on this finding we propose that the development of L-type calcium channels can be considered as one of the factors determining the different physiological properties of fibre types.

Topics: Aging; Animals; Animals, Newborn; Boron Compounds; Calcium; Calcium Channels, L-Type; Dihydropyridines; Fluorescent Dyes; Gene Expression Regulation, Developmental; Glycolysis; Intracellular Membranes; Mice; Muscle Fibers, Fast-Twitch; Muscle Fibers, Slow-Twitch; Muscle Proteins; Muscle, Skeletal; Oxidation-Reduction; Oxygen Consumption; Succinate Dehydrogenase