| Autor: |
Wakimoto, Koji, Kobayashi, Kinji, Kuro-o, Makoto, Yao, Atsushi, Iwamoto, Takahiro, Yanaka, Noriyuki, Kita, Satomi, Nishida, Atsuyuki, Azuma, Sadahiro, Toyoda, Yutaka, Omori, Kenji, Imahie, Hiroshi, Oka, Toru, Kudoh, Sumiyo, Kohmoto, Osami, Yazaki, Yoshio, Shigekawa, Munekazu, Imai, Yuji, Nabeshima, Yo-ichi, Komuro, Issei |
| Zdroj: |
Journal of Biological Chemistry; November 2000, Vol. 275 Issue: 47 p36991-36998, 8p |
| Abstrakt: |
Ca2+, which enters cardiac myocytes through voltage-dependent Ca2+channels during excitation, is extruded from myocytes primarily by the Na+/Ca2+exchanger (NCX1) during relaxation. The increase in intracellular Ca2+concentration in myocytes by digitalis treatment and after ischemia/reperfusion is also thought to result from the reverse mode of the Na+/Ca2+exchange mechanism. However, the precise roles of the NCX1 are still unclear because of the lack of its specific inhibitors. We generated Ncx1-deficient mice by gene targeting to determine the in vivofunction of the exchanger. Homozygous Ncx1-deficient mice died between embryonic days 9 and 10. Their hearts did not beat, and cardiac myocytes showed apoptosis. No forward mode or reverse mode of the Na+/Ca2+exchange activity was detected in null mutant hearts. The Na+-dependent Ca2+exchange activity as well as protein content of NCX1 were decreased by ∼50% in the heart, kidney, aorta, and smooth muscle cells of the heterozygous mice, and tension development of the aortic ring in Na+-free solution was markedly impaired in heterozygous mice. These findings suggest that NCX1 is required for heartbeats and survival of cardiac myocytes in embryos and plays critical roles in Na+-dependent Ca2+handling in the heart and aorta. |
| Databáze: |
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