Na+/Ca2+ exchanger-deficient mice have disorganized myofibrils and swollen mitochondria in cardiomyocytes.
The Na(+)/Ca(2+) exchanger (NCX1) plays a key role in maintaining Ca(2+) homeostasis in cardiomyocytes. Disruption of Ncx1 gene in mice results in embryonic lethality between embryonic day 9 and 10, with the mice lacking spontaneous heartbeats. We examined the mechanism of lack of heartbeats in Ncx1-deficient mice. Ultrastructual analysis demonstrated that Ncx1-deficient mice showed severe disorganization of myofibrils, a lack of Z-lines and swelling of mitochondria in cardiomyocytes. However, the expressions of cardiac-specific genes including transcription factor genes and contractile protein genes were not changed in Ncx1-deficient mice. Abnormal Ca(2+) handling itself or the lack of heartbeats due to the inactivation of Ncx1 gene may cause the disorganization of myofibrillogenesis. Although NCX1 protein levels were decreased in heterozygous mice, there were no changes in NCX2 and NCX3 protein levels between wild type and heterozygous mice.
Wakimoto
Koji
K
Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd, 3-16-89 Kashima, Yodogawa-ku, Osaka 532-8505, Japan. wakimoto@tanabe.co.jp
Fujimura
Hisako
H
Iwamoto
Takahiro
T
Oka
Toru
T
Kobayashi
Kinji
K
Kita
Satomi
S
Kudoh
Sumiyo
S
Kuro-o
Makoto
M
Nabeshima
Yo ichi
Yi
Shigekawa
Munekazu
M
Imai
Yuji
Y
Komuro
Issei
I
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation; D006321:Heart; D007668:Kidney / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D032383:Myocytes, Cardiac / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D009210:Myofibrils / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019831:Sodium-Calcium Exchanger / Q000032:analysis / Q000235:genetics / Q000502:physiology*
C491739:Slc8a2 protein, mouse; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1