Changes in thyroid state affect pHi and Nai+ homeostasis in rat ventricular myocytes.
Changes in thyroid state affect pHi and Nai+ homeostasis in rat ventricular myocytes.
复制标题
甲状腺状态的变化影响大鼠心室肌细胞的 pHi 和 Nai 稳态。
DOI：
10.1006/jmcc.1997.0495
复制
发表时间：
1997
影响因子：
5
通讯作者：
Solaro,RJ
中科院分区：
文献类型：
--
作者：
Wolska,BM;Averyhart-Fullard,V;Omachi,A;Stojanović,MO;Kallen,RG;Solaro,RJ
我们已经验证了甲状腺状态可能通过影响细胞内pH（pHi）和Na+（Nai+）来影响细胞内Ca 2+的流动和肌丝对Ca 2+的反应的假设。从甲状腺功能减退、甲状腺功能正常和甲状腺功能亢进动物分离的单个心肌细胞用fura-2/AM（Cai 2+探针）、BCECF/AM（pHiprobe）或SBFI/AM（Nai+探针）加载。与甲状腺功能减退动物相比，从甲状腺功能亢进大鼠心脏分离的心肌细胞表现出显著的：（1）缩短程度增加;（2）收缩峰值时间减少;（3）fura-2荧光比率的峰值幅度增加;（4）pHi降低（ΔpHi=0.19±0.05）;（5）Nai+增加（ΔNai+=2.88±0.55 mm）。我们还比较了pHin Langendorff灌注甲状腺功能减退和甲状腺功能亢进大鼠心脏使用NMR。我们发现甲状腺功能亢进的心脏比甲状腺功能减退的心脏酸性高0.15±0.03个pH单位。mRNA水平的分析表明，甲亢增加了Na+/Ca 2+交换和Na+/H+逆向转运蛋白的表达，降低了Na+通道mRNA的表达。这些变化似乎是Nai+和pHi变化的部分原因。我们的研究结果提供了第一个证据表明，与甲状腺状态改变相关的心肌收缩力的变化不仅涉及对Ca 2+的影响，而且还可能涉及肌丝对Cai 2+的反应的变化，Cai 2+由改变的pH和Nai+介导。
We have tested the hypothesis that thyroid state may influence both the flow of cellular Ca2+and the myofilament response to Ca2+by effects on intracellular pH (pHi) and Na+(Nai+). Single cardiac myocytes isolated from hypothyroid, euthyroid and hyperthyroid animals were loaded with fura-2/AM (Cai2+probe), BCECF/AM (pHiprobe) or SBFI/AM (Nai+probe). Compared with hypothyroid animals, myocytes isolated from hyperthyroid rat hearts demonstrated a significant: (1) increase in extent of shortening; (2) decrease in the time to peak contraction; (3) increase in the peak amplitude of the fura-2 fluorescence ratio; (4) decrease in pHi(ΔpHi=0.19±0.05); and (5) increase in Nai+(ΔNai+=2.88±0.55 mm). We have also compared pHiin Langendorff perfused hypo- and hyperthyroid rat hearts using NMR. We have found that hyperthyroid hearts are 0.15±0.03 pH units more acidic than hypothyroid hearts. Analysis of mRNA levels demonstrated that hyperthyroidism increased expression of both the Na+/Ca2+exchanger and Na+/H+antiporter, and decreased expression of Na+channel mRNAs. These changes appear partially responsible for the observed changes in Nai+and pHi. Our results provide the first evidence that changes in cardiac contractility associated with altered thyroid state not only involve effects on Ca2+, but may also involve changes in the response of the myofilaments to Cai2+mediated by altered pHiand Nai+.