Modulation of the calcium release channel/ryanodine receptor from skeletal muscle by energy charge

In this paper, we describe the modulatory role of different proportions of adenine nucleotides such as AMP, ADP and ATP, in the activation of the sarcoplasmic reticulum ryanodine receptor. The proportion of the adenine nucleotides was expressed in terms of the metabolic control parameter known as energy charge. Using the specific binding assay of [3H]ryanodine as a probe of the functional state of the ryanodine receptor, it was observed that the activation promoted by physiological [ATP] was positively modulated by AMP and ADP, also assayed at physiological concentrations. Ryanodine receptor was fully activated by energy charge values above 0.84. Considering the energy charge experiments, the ryanodine receptor activation cannot be explained exclusively in terms of an ATP effect, but by the coordinated action of the three nucleotides. The data suggest that adenine nucleotides, present at physiological levels, exerted a complex regulation in the ryanodine receptor.