- 著者
- Nagasaka Shiro Katoh Hideki Niu Chim Feng Matsui Saori Urushida Tsuyoshi Satoh Hiroshi Watanabe Yasuhide Hayashi Hideharu
- 出版者
- 社団法人日本循環器学会
- 雑誌
- Circulation journal : official journal of the Japanese Circulation Society (ISSN:13469843)
- 巻号頁・発行日
- vol.71, no.3, pp.429-436, 2007-02-20
- 被引用文献数
- 2 23
Background The identification of protein kinase A(PKA) anchoring proteins on mitochondria implies a direct effect of PKA on mitochondrial function. However, little is known about the relationship between PKA and mitochondrial metabolism. Methods and Results The effects of PKA on the mitochondrial redox state(flavin adenine dinucleotide(FAD)), mitochondrial membrane potential(ΔΨ_m) and reactive oxygen species(ROS) production were investigated in saponin-permeabilized rat cardiomyocytes. The PKA catalytic subunit(PKA_<cat>; 50 unit/ml) increased FAD intensities by 56.6±7.9%(p<0.01), 2'7'-dichlorofluorescin diacetate(DCF) intensities by 10.5±3.3 fold(p<0.01) and depolarized ΔΨ_m to 48.1±9.5% of the control(p<0.01). Trolox(a ROS scavenger; 100μmol/L) inhibited PKA_<cat>-induced ΔΨ_m, FAD and DCF alteration. PKA_<cat>-induced ΔΨ_m depolarization was inhibited by an inhibitor of the inner membrane anion channel(IMAC), 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid(DIDS: 1μmol/L) but not by an inhibitor of mitochondrial permeability transition pore(mPTP), cyclosporine A(lOOnmol/L). Conclusions PKA_<cat> alters FAD and ΔΨ_m via mitochodrial ROS generation, and PKAcat-induced ΔΨ_m depolarization was not caused by mPTP but rather by DIDS-sensitive mechanisms, which could be caused by opening of the IMAC. The effects of PKA on mitochondrial function could be related to myocardial function under the condition of extensive β-adrenergic stimulation.