Enhanced activity of ventricular Na+-HCO3- cotransport in pressure overload hypertrophy.
Enhanced activity of ventricular Na+-HCO3- cotransport in pressure overload hypertrophy.
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DOI：
10.1152/ajpheart.00964.2006
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发表时间：
2007-08
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影响因子：
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通讯作者：
Taku Yamamoto;T. Shirayama;T. Sakatani;Tomosaburo Takahashi;Hideo Tanaka;T. Takamatsu;K. Spitzer;H. Matsubara
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文献类型：
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作者：
Taku Yamamoto;T. Shirayama;T. Sakatani;Tomosaburo Takahashi;Hideo Tanaka;T. Takamatsu;K. Spitzer;H. Matsubara
Na（+）-HCO（3）（-）协同转运蛋白（NBC）在正常心室肌细胞内pH（pH（i））调节中起关键作用。然而，NBC在非缺血性肥厚心脏中的状态尚未得到解决。在这项研究中，我们研究了NBC在成年大鼠心室肌细胞的功能和分子特性。从正常和肥大的心脏中酶促分离细胞。通过肾上腹主动脉缩窄50%持续7周造成的压力超负荷诱导心室肥厚。使用荧光pH指示剂2 '，7'-双（2-羧乙基）5-（6）羧基荧光素在单细胞中测量pH（i）。实时定量PCR分析用于定量评估NBC编码mRNA的表达，包括SLC 4A 4（编码电生NBC，NBCe 1）和SLC 4A 7（电中性NBC，NBCn 1）。我们的结果表明：1）主动脉缩窄使NBC的生电NBCe 1（SLC 4A 4）和电中性NBCn 1（SLC 4A 7）形式的mRNA水平增加，2）NBC上调发生在缩窄后3天内，3）正常和肥大心室显示NBC表达的区域差异，4）肥大心肌细胞中通过NBC的酸排出（J（NBC））显著增加，5）虽然肥大心肌细胞通过Na（+）/H（+）交换的酸排出也增加，但J（NBC）的相对增强更大; 6）膜去极化显著增加肥大心肌细胞的J（NBC）; 7）血管紧张素Ⅱ AT（1）受体拮抗剂氯沙坦显著减弱主动脉缩窄3周引起的两种NBC的上调。在肥大发育过程中增强的NBC活性提供了细胞内Na（+）过载的机制，这可能使心室在缺血-再灌注期间更容易受到Ca（2+）过载的影响。
The Na(+)-HCO(3)(-) cotransporter (NBC) plays a key role in intracellular pH (pH(i)) regulation in normal ventricular muscle. However, the state of NBC in nonischemic hypertrophied hearts is unresolved. In this study, we examined functional and molecular properties of NBC in adult rat ventricular myocytes. The cells were enzymatically isolated from both normal and hypertrophied hearts. Ventricular hypertrophy was induced by pressure overload created by suprarenal abdominal aortic constriction of 50% for 7 wk. pH(i) was measured in single cells using the fluorescent pH indicator 2',7'-bis(2-carboxyethyl)5-(6)carboxyfluorescein. Real-time PCR analysis was used to quantitatively assess expression of NBC-encoding mRNA, including SLC4A4 (encoding electrogenic NBC, NBCe1) and SLC4A7 (electroneutral NBC, NBCn1). Our results demonstrate that: 1) mRNA levels of both the electrogenic NBCe1 (SLC4A4) and electroneutral NBCn1 (SLC4A7) forms of NBC were increased by aortic constriction, 2) the onset of NBC upregulation occurred within 3 days after constriction, 3) normal and hypertrophied ventricles displayed regional differences in NBC expression, 4) acid extrusion via NBC (J(NBC)) was increased significantly in hypertrophied myocytes, 5) although acid extrusion via Na(+)/H(+) exchange was also increased in hypertrophied myocytes, the relative enhancement of J(NBC) was larger, 6) membrane depolarization markedly increased J(NBC) in hypertrophied myocytes, and 7) losartan, an ANG II AT(1) receptor antagonist, significantly attenuated the upregulation of both NBCs induced by 3 wk of aortic constriction. Enhanced NBC activity during hypertrophic development provides a mechanism for intracellular Na(+) overload, which may render the ventricles more vulnerable to Ca(2+) overload during ischemia-reperfusion.