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Alterations in intracellular free Ca2+ handling in mouse models for Duchenne muscular dystrophy
Author(s) -
Mazala Davi Augusto,
English Samuel Andrew,
Chen Dapeng,
Chin Eva R
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb599
Subject(s) - duchenne muscular dystrophy , mdx mouse , muscular dystrophy , utrophin , stimulation , dystrophin , endocrinology , medicine , chemistry , intracellular , calcium , calcium in biology , skeletal muscle , biochemistry
Duchenne muscular dystrophy (DMD) is a progressive degenerative muscle disease that affects 1 out of 3500 boys. It is known that the mouse model most frequently used in DMD research, the mdx mice, upregulates utrophin (utr), a protein with similar roles as dystrophin. Thus, the mdx /utr −/− double mutant (DM) is an alternative model that may be a more appropriate model for studying DMD disease mechanisms. One proposed mechanism behind the disease progression is related to poor intracellular calcium ([Ca 2+ ] i ) handling. The purpose of the current study was to evaluate the [Ca 2+ ] i levels in response to repeated tetanic stimulation in intact single muscle fibres from the DM mouse model in comparison to fibres from mdx mice. Single muscle fibres were obtained from the flexor digitorum brevis by collagenase digestion and loaded with Fura‐2 AM for [Ca 2+ ] i assessment at a range of stimulation frequencies (10, 30, 50, 70, 100, 120 and 150Hz). There were no differences for peak Fura‐2 ratio at any of the stimulation frequencies but the resting Fura‐2 ratio was reduced in the DM compared to the mdx mice (0.361±0.029 vs 0.381±0.019; p<0.05). The diameter and length of muscle fibres from DM were smaller compared to the mdx group (p<0.05). Furthermore, 65% of the fibres from DM animals failed to maintain peak Ca 2+ during a tetanus, while 43% of the mdx fibres failed. These data suggest that alterations in the Ca 2+ handling properties may be due to plasma or t‐tubule membrane conductance abnormalities and/or impaired Ca 2+ release or storage by the sarcoplasmic reticulum. This project has been funded by Department of Kinesiology Graduate Research Initiative Project (GRIP).