The overall objective of this project is to gain deeper understanding of fiber type-specific gene expression skeletal muscle and of calcium signalling in muscle and neurons. Activity dependent gene expression will be studied in skeletal muscle and role of cytosolic [Ca/2+] in such """"""""excitation-transcription"""""""" (ET) coupling will be determined. Understand of the mechanisms of ET coupling is of central importance for maintenance of muscle tone and function in health, inactivity and after traumatic nerve section or during neuromuscular disease. The subcellular details of calcium signaling will be explored in isolated neurons to explain important local effects of [Ca/2+] relevant to wide range of neuronal functions. The contributions of Ca/2+ transport systems and Ca/2+ binding proteins to the decline of muscle [Ca/2+] after Ca/2+ release, which is crucial to the relaxation of normal and diseased muscle, will be determined for both fast-and slow-twitch muscle. Chronic electrical stimulation will be used to study plasticity of gene expression in individual enzymatically isolated adult mouse skeletal muscle fibers in culture. The localization and functional properties of the calcium uptake, storage, and release organelles in neurons will be determined by high spatio-temporal resolution confocal microscopy of individual sympathetic ganglion neurons. Protein isoform composition will be determined in the same individual muscle fibers from which [Ca/2+] transients were recorded to define the molecular basis for the diversity of calcium removal mechanisms in fibers of the same and different types. These studies will provide a better understanding of the cellular and molecular mechanisms underlying fiber type conversion in skeletal muscle, the control of a variety of calcium dependent processes in both muscle and neurons, and relaxation of skeletal muscle fibers. They will provide deeper insight into calcium regulation and its adaptability in muscle and neurons under a variety of physiological states as well as during disuse, aging and under possible pathological conditions.
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