Takebayashi Satoshi, Li Yulong, Kaku Toshihiko, Inagaki Shuichiro, Hashimoto Yutaka, Kimura Kazuhiro, Miyamoto Shinji, Hadama Tetsuo, Ono Katsushige
Department of Cardiovascular Science, Oita University School of Medicine, Oita 879-5593, Japan.
Biochem Biophys Res Commun. 2006 Jun 30;345(2):766-73. doi: 10.1016/j.bbrc.2006.04.146. Epub 2006 May 5.
We utilized Wistar rats with monocrotaline (MCT)-induced right ventricular hypertrophy (RVH) in order to evaluate the T-type Ca2+ channel current (ICaT) for myocardial contraction. RT-PCR provides that mRNA for T-type Ca2+ channel alpha1-subunits in hypertrophied myocytes was significantly higher than those in control rats (alpha1G; 264+/-36%, alpha1H; 191+/-34%; P<0.05). By whole-cell patch-clamp study, ICaT was recorded only in hypertrophied myocytes but not in control myocytes. The application of 50 nmol/L nifedipine reduced the twitch tension of the right ventricles equally in the control and RVH rats. On the other hand, 0.5 micromol/L mibefradil, a T-type Ca2+ channel blocker, strongly inhibited the twitch tension of the RVH muscle (control 6.4+/-0.8% vs. RVH 20.0+/-2.3% at 5 Hz; P<0.01). In conclusion, our results indicate the functional expression of T-type Ca2+ channels in the hypertrophied heart and their contribution to the remodeling of excitation-contraction coupling in the cardiac myocyte.
为了评估心肌收缩时的T型Ca2+通道电流（ICaT），我们使用了用野百合碱（MCT）诱导右心室肥厚（RVH）的Wistar大鼠。逆转录聚合酶链反应（RT-PCR）显示，肥厚心肌细胞中T型Ca2+通道α1亚基的mRNA显著高于对照大鼠（α1G；264±36%，α1H；191±34%；P<0.05）。通过全细胞膜片钳研究，仅在肥厚心肌细胞中记录到ICaT，而在对照心肌细胞中未记录到。应用50 nmol/L硝苯地平可同等程度降低对照和RVH大鼠右心室的收缩张力。另一方面，0.5 μmol/L米贝地尔，一种T型Ca2+通道阻滞剂，可强烈抑制RVH肌肉的收缩张力（5 Hz时，对照为6.4±0.8%，RVH为20.0±2.3%；P<0.01）。总之，我们的结果表明肥厚心脏中T型Ca2+通道的功能性表达及其对心肌细胞兴奋-收缩偶联重塑的作用。
