Calcium Both Activates and Inactivates Calcium Release from Cardiac Sarcoplasmic Reticulum

Abstract

Ringer reported that ventricular contraction ceases within 20 min in the presence of a Ca^{2 +} - free saline solution and is restored by the addition of a Ca²⁺ salt [30]. Although this most frequently quoted article does not indicate the animal species from which the ventricle was taken, a previous paper indicated that the frog ventricle was used [29]. These articles by Ringer have been widely quoted to demonstrate the importance of transsarcolemmal Ca^{2 +} influx in controlling cardiac contraction, not only in the frog ventricular tissue but in mammalian cardiac tissue as well. Repeating Ringer’s experiments on small trabeculae from the frog ventricle, but with observation under the high-power microscope, confirmed Ringer’s findings. Not only was contraction abolished within 2-3 min by Ca²⁺ removal, but microscopic examination found the preparation to be completely quiescent. In contrast, when the experiments were done in a mammalian (e. g., adult rat) ventricular tissue, Ca²⁺ removal resulted in an almost complete abolition of the contraction detected from the ends of the trabecula with a highly sensitive transducer but observation under the microscope showed localized cyclic contractions. This very prominent but desynchronized contractile behavior persisted for many hours in a Ca^{2 +} -free solution (A. Fabiato, unpublished observations). This observation is one of many pieces of evidence suggesting that, in addition to the transsarcolemmal Ca²⁺ influx, an intracellular Ca²⁺ store participates in the excitation- contraction coupling of the adult mammalian cardiac tissue. Other experiments have demonstrated that the Ca²⁺ store is located in the sarcoplasmic reticulum (SR) [7,15].