Résumé :
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Communication n° 618 In skeletal muscle, Ca2+ is implicated in contraction and in regulation of gene expression. An alteration of [Ca2+]i homeostasis is responsible, at least partially, of the muscle degeneration that occurs after eccentric contractions in Duchenne muscular dystrophy, a disease characterised by the loss of a cytoskeletal protein called dystrophin. In a previous work, using the patch-clamp technique (cell-attached configuration, 110 mM Ca2+ in the pipette), we showed the presence of voltage-independent Ca2+ channels in isolated flexor digitorum brevis (FDB) fibres. These channels were sensitive to calcium stores depletion by thapsigargin or caffein (SOCs: store-operated channel). They had a conductance of 8 pS and a reversal potential of +50 mV. They were poorly selective (slightly more permeable to Ca2+ than to K+, PCa/PK = 1.3). Thapsigargin did not modify these properties but increased the occurrence of these channels and their open probability. In dystrophic muscle fibres, these channels were abnormally activated in adult dystrophic (mdx) skeletal mucle fibers, suggesting a possible deregulation due to the lack of dystrophin and thus involving the cytoskeleton. In order to study this regulation, we investigated if those channels were mechanosensitive. Applying a negative pressure to the patch electrode increased the quantity of charges passing through these channels. The effects of thapsigargin and stretch were additive. The stretch-activated channels (SACs) detected in these conditions had the same unitary conductance and the same reversal potential as the SOCs. A pharmacological approach with gadolinium, SFK93635 and streptomycin was then used to distinguish whether SOCs are mechanosensitive or whether these SOCs and SACs represent two populations of channels with common properties.
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