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Elevated free Ca2+ concentrations found in adult dystrophic muscle fibers result in enhanced protein degradation. Since the difference in concentrations may reflect differences in entry, Ca2+ leak channels in cultures of normal and Duchenne human myotubes, and normal and mdx murine myotubes, have been identified and characterized. The open probability of(More)
The defective gene responsible for Duchenne muscular dystrophy in humans and the dystrophic condition in mdx mice results in a lack of dystrophin at first thought to be localized to the triads, but more recently found on the cytoplasmic side of the sarcolemma of skeletal muscle fibres. Because the total calcium content of dystrophic fibres is significantly(More)
We examined pathways which might result in the elevated resting free calcium [( Ca2+]i) levels observed in dystrophic mouse (mdx) skeletal muscle fibers and myotubes and human Duchenne muscular dystrophy myotubes. We found that mdx fibers, loaded with the calcium indicator fura-2, were less able to regulate [Ca2+]i levels in the region near the sarcolemma.(More)
There are conflicting reports regarding whether resting free calcium levels ([Ca2+]i) are elevated in dystrophic mouse (mdx) myotubes and adult myofibers. We reinvestigated this question and found several lines of evidence supporting the hypothesis that increased calcium influx via leak channels leads to increases in resting [Ca2+]i. 1) Step calibration of(More)
The present studies were carried out to evaluate the mechanisms by which PTH/PTHrP receptor (PTHR) activation influences cell viability. In 293 cells expressing recombinant PTHRs, PTH treatment markedly reduced the number of viable cells. This effect was associated with a marked apoptotic response including DNA fragmentation and the appearance of apoptotic(More)
Fertilization of the sea urchin egg stimulates a wave of exocytosis of cortical vesicles, but the mechanism by which fertilization regulates this secretion is not fully understood. We describe here experiments which suggest that polyphosphoinositide metabolism could be a factor in this regulation. We find that the cortical vesicle exocytosis in the egg of(More)
The plasma membrane calcium extrusion mechanism, PMCA (plasma membrane calcium ATPase) isoform 2 is richly expressed in the brain and particularly the cerebellum. Whilst PMCA2 is known to interact with a variety of proteins to participate in important signalling events [Strehler EE, Filoteo AG, Penniston JT, Caride AJ (2007) Plasma-membrane Ca(2+) pumps:(More)
To investigate the roles of inositol 1,4,5-trisphosphate (InsP3) and guanyl nucleotide binding proteins (G-proteins) in the transduction mechanism coupling fertilization and exocytosis of cortical vesicles in sea urchin eggs, we microinjected InsP3 and guanyl nucleotide analogs into eggs of Lytechinus variegatus. Injection of 28 nM InsP3 caused exocytosis.(More)
The mechanisms of ligand binding and receptor activation for G-protein-coupled receptors in the secretin/parathyroid hormone (PTH) receptor subfamily are not understood. The PTH1 receptor (PTH1R) signals in response to both PTH and parathyroid hormone-related peptide (PTHrP), whereas the PTH2 receptor (PTH2R) responds only to PTH, not to PTHrP. To locate(More)