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Calcium-Dependent Activation of Skeletal-Muscle Ca2+ Release Channel (Ryanodine Receptor) by Calmodulin

https://doi.org/10.1006/bbrc.1995.2238Get rights and content

Abstract

In this study terminal cisternae vesicles from rabbit skeletal muscle were fused into planar bilayers and the effect of calmodulin on single Ca2+ release channel currents was investigated. In the presence of 10−7 and 10−9 M free [Ca2+], nanomolar concentrations of calmodulin activated the channel by increasing the open probability of single-channel events in a dose dependent manner. The activatory effect of calmodulin was reversed by 10 μM ruthenium red. At 10−5 M free [Ca2+], calmodulin (0.1-1 μM) inhibited channel activity. Calmodulin overlays were carried out using concentrations of Ca2+ similar to those used for the planar lipid bilayer assays. In the presence of 10−7 M [Ca2+], calmodulin bound to the ryanodine receptor, to a region defined by residues 2937-3225 and 3546-3655. These results suggest that calmodulin may activate the Ca2+-release channel (ryanodine-receptor) by interacting with binding sites localized in the central portion of the RYR protomer.

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