title: Increased O2 consumption in excitation-contraction coupling in hypertrophied rat heart slices related to increased Na+ -Ca2+ 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. O(2) consumption per minute (mVO(2)) of mechanically unloaded left ventricular slices was measured in the absence and presence of 1-Hz field stimulation. Basal metabolic mVO(2), i.e., mVO(2) without electrical stimulation, was significantly smaller, but mVO(2) for the total Ca(2+) handling in excitation-contraction coupling (E-C coupling mVO(2)), i.e., delta mVO(2) (=mVO(2) with stimulation - mVO(2) 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 Ca(2+)-ATPase (SERCA2) was depressed by 40%; mVO(2) consumed by the Na(+)/K(+)-ATPase (NKA)-Na(+)/Ca(2+) exchange (NCX) coupling was increased by 100%. The depressed mVO(2) consumption by SERCA2 was supported by lower protein expressions of phosphorylated-Ser(16) phospholamban and SERCA2. The increase in NKA-NCX coupling mVO(2) 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 mVO(2) in hypertrophy was derived from decreased SERCA2 activity (1ATP: 2Ca(2+)) and increased NCX activity coupled to NKA activity (1ATP: Ca(2+)). Taken together, we conclude that the energetically less efficient Ca(2+) extrusion pathway evenly contributes to Ca(2+) handling in E-C coupling in the present hypertrophy model.
authors.affiliation: Department of Physiology II, Nara Medical University, Kashihara, 634-8521, Japan.
authors.forename: Juichiro
authors.initials: J
authors.lastname: Shimizu
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamashita
authors.forename: Hiromi
authors.initials: H
authors.lastname: Misawa
authors.forename: Kiyoe
authors.initials: K
authors.lastname: Tohne
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsuoka
authors.forename: Bongju
authors.initials: B
authors.lastname: Kim
authors.forename: Ayako
authors.initials: A
authors.lastname: Takeuchi
authors.forename: Chikako
authors.initials: C
authors.lastname: Nakajima-Takenaka
authors.forename: Miyako
authors.initials: M
authors.lastname: Takaki