Large-Scale Structural Changes in the Sarcoplasmic Reticulum ATP-ASE are Essential for Calcium Active Transport

Abstract

The active (energy-dependent) transport of calcium from the cytoplasm across the sarcoplasmic reticulum (SR) membrane into the sarcotubular system by the membrane Ca²⁺ATPase is responsible for the relaxation phase of the contraction-relaxation cycle in striated and cardiac muscle (Ebashi et al., 1969). Since the sarcoplasmic retículum membrane can be isolated in the form of closed unilamellar vesicles in which the Ca²⁺ATPase comprises over 90% of the membrane protein (Meissner et al., 1973), the enzyme catalyzed chemical reactions involved in the calcium active transport process (DeMeis and Vienna, 1979), and the structure and organization of the membrane components (Blasie et al., 1985) have been relatively well characterized. As a result, this system provides an excellent prototype for the study of the critical structure-function relationships involved in the active transport of ions across biological membranes.

Two Ca²⁺ ions per protein molecule are bound to all forms of the ATPase enzyme referred to in this paper. To simplifiy the notation, the Ca²⁺ ions have been omitted, i.e., the first phosphorylated intermediate, for example, is denoted as E₁~P instead of (Ca²⁺)₂E₁~P.