Measurement of RyR permeability reveals a role of calsequestrin in termination of SR Ca release in skeletal muscle

The intracellular signal for contraction of skeletal muscle is the rapid increase in free cytosolic [Ca]. This increase requires coordinated opening of a substantial fraction of intracellular Ca release channels of the SR, which allows for a large flux of Ca from stores to cytosol. This flux must terminate rapidly as well to allow for the fast decay of [Ca] required for mechanical relaxation. The mechanisms that terminate Ca release flux may include both a reduction in the openness of the release channels and a reduction in the current per channel, as the SR depletes and the driving force for Ca flux is reduced. The relative contribution of such gating and depletion processes is not known quantitatively for skeletal muscle. In cardiac muscle, where more is known, an interaction has been demonstrated whereby depletion reduces flux both directly, by reducing the [Ca] gradient,