ORIGINAL PAPER Increased O 2 consumption in excitation–contraction coupling in hypertrophied rat heart slices related to increased Na + –Ca 2+ exchange activity Juichiro Shimizu Æ Daisuke Yamashita Æ Hiromi Misawa Æ Kiyoe Tohne Æ Satoshi Matsuoka Æ Bongju Kim Æ Ayako Takeuchi Æ Chikako Nakajima-Takenaka Æ Miyako Takaki Received: 26 August 2008 / Accepted: 31 October 2008 / Published online: 11 December 2008 Ó The Physiological Society of Japan and Springer 2008 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 hypertro- phied 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 excita- tion–contraction coupling (E–C coupling mVO 2 ), i.e., delta mVO 2 (=mVO 2 with stimulation - mVO 2 without stimu- lation), 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) cou- pling 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. Keywords Ca 2? handling Á Excitation–contraction coupling Á Na ? /Ca 2? exchanger Á Oxygen consumption Á Sarcoplasmic reticulum Ca 2? -ATPase Abbreviations BDM 2,3-Butanedione monoxime BW Body weight CE 5-(and -6)-Carboxyeosin diacetate CONT Saline-infused normal hearts CPA Cyclopiazonic acid DMSO Dimethyl sulfoxide Dob Dobutamine DW Dry weight E–C coupling Excitation–contraction coupling 1st NT 1st Measurement value in normal Tyrode solution HYP Isoproterenol-infused hypertrophic hearts KBR KB-R7943 LV Left ventricle MAPK Mitogen-activated protein kinase MKK MAPK kinase MTC Masson’s trichrome mVO 2 O 2 consumption per minute NCX Na ? /Ca 2? exchanger NFAT Nuclear factor of activated T cells NHE Na ? /H ? exchanger J. Shimizu Á D. Yamashita Á H. Misawa Á K. Tohne Á C. Nakajima-Takenaka Á M. Takaki (&) Department of Physiology II, Nara Medical University, 840 Shijo-Cho, Kashihara 634-8521, Japan e-mail: mtakaki@naramed-u.ac.jp S. Matsuoka Á B. Kim Á A. Takeuchi Department of Physiology and Biophysics, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan 123 J Physiol Sci (2009) 59:63–74 DOI 10.1007/s12576-008-0006-6