Role of NCX in increased O2 consumption in hypertrophied rat hearts

Abstract

The aim of the present study was to prove the different energetics in isoproterenol-induced hypertrophied hearts compared to normal hearts. Myocardial O₂ consumption per minute (mVO₂) in myocardial slices was measured without and with 1-Hz field stimulation (stim.). mVO₂ without stim. corresponds to basal metabolic mVO₂. Delta mVO₂ (= mVO₂ with stim.-mVO₂without stim.) corresponds to O₂ consumption in excitation-contraction (E-C) coupling. Basal metabolic mVO₂ was significantly smaller but delta mVO₂ was significantly larger in the hypertrophy. Na⁺-Ca²⁺ exchange (NCX1) current was markedly increased associated with depressed sarcoplasmic reticulum Ca²⁺ ATPase (SERCA2) activity due to decreased phospho-Ser¹⁶ phospholamban expression, resulting in the increase of delta mVO₂. Since the NCX1 protein expression level did not increase, the marked increase in NCX1 current is attributable, at least in part, to attenuation of the intrinsic inactivation mechanisms of NCX1. It is plausible that decreased basal metabolic mVO₂ is due to depressed Na⁺/K⁺ ATPase (NKA) expression and/or activity because of phospholemman overexpression in this hypertrophy. However, measured NKA current was not decreased. We concluded that the different origin of the O₂ consumption in E-C coupling in the hypertrophy was derived from decreased SERCA2 activity (1ATP: 2Ca²⁺) and increased NCX activity coupled to NKA activity (1ATP: Ca²⁺). [J Physiol Sci. 2008;58 Suppl:S184]