Osmotic responses demonstrating the extracellular character of the sarcoplasmic reticulum.

1. Changes in the dimensions of the sarcoplasmic reticulum in frog sartorius muscles exposed to hypertonic and hypotonic solutions have been studied with the electron microscope.2. The volume of the sarcoplasmic reticulum has been found to be linearly related with a negative slope to the reciprocal of the osmotic pressure. Over the range 0.75 to 3.5 x normal osmotic pressure the reticulum volume has been calculated to change from 11.5 to 18.5% of normal cell volume.3. These changes in sarcoplasmic reticulum volume correspond to the calculated changes in the volume of the intra-fibre sucrose compartment, postulated by earlier workers on the basis of studies on changes in cell volume with changes in osmotic pressure in living muscles.4. To explain these and other related findings on the distribution of electrolytes in muscle, it is proposed that the sarcoplasmic reticulum of skeletal muscle is an extracellular compartment.5. The significance of this hypothesis for the mechanism of excitation-contraction coupling is discussed.