Increased O2 consumption in excitation-contraction coupling in hypertrophied rat heart slices related to increased Na+-Ca 2+ exchange activity

Abstract

The goal of our study was to evaluate the origin of the increased O 2 consumption in electrically stimulated left ventricular slices of isoproterenol-induced hypertrophied rat hearts with normal left ventricular pressure. O2 consumption per minute (mVO2) of mechanically unloaded left ventricular slices was measured in the absence and presence of 1-Hz field stimulation. Basal metabolic mVO2, i.e., mVO2 without electrical stimulation, was significantly smaller, but mVO2 for the total Ca2+ handling in excitation-contraction coupling (E-C coupling mVO2), i.e., delta mVO2 (=mVO2 with stimulation - mVO2 without stimulation), was significantly larger in the hypertrophied heart. Furthermore, the fraction of E-C coupling mVO 2 was markedly altered in the hypertrophied heart. Namely, mVO 2 consumed by sarcoplasmic reticulum Ca2+-ATPase (SERCA2) was depressed by 40%; mVO2 consumed by the Na+/K +-ATPase (NKA)-Na+/Ca2+ exchange (NCX) coupling was increased by 100%. The depressed mVO2 consumption by SERCA2 was supported by lower protein expressions of phosphorylated-Ser16 phospholamban and SERCA2. The increase in NKA-NCX coupling mVO2 was supported by marked augmentation of NCX current. However, the increase in NCX current was not due to the increase in NCX1 protein expression, but was attributable to attenuation of the intrinsic inactivation mechanisms. The present results demonstrated that the altered origin of the increased E-C coupling mVO2 in hypertrophy was derived from decreased SERCA2 activity (1ATP: 2Ca2+) and increased NCX activity coupled to NKA activity (1ATP: Ca2+). Taken together, we conclude that the energetically less efficient Ca2+ extrusion pathway evenly contributes to Ca2+ handling in E-C coupling in the present hypertrophy model. © 2008 The Physiological Society of Japan and Springer.