Effect of mitochondrial and plasma membrane potentials on accumulation of hexakis (2-methoxyisobutylisonitrile) technetium(I) in cultured mouse fibroblasts.
Effect of mitochondrial and plasma membrane potentials on accumulation of hexakis (2-methoxyisobutylisonitrile) technetium(I) in cultured mouse fibroblasts.
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发表时间：
1990-10
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通讯作者：
M. L. Chiu;J. Kronauge;D. Piwnica-worms
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作者：
M. L. Chiu;J. Kronauge;D. Piwnica-worms
六（2-甲氧基异丁基异腈）锝(I) （Tc-MIBI）是一类以99mtc为基础的亲脂性阳离子心肌灌注显像剂的代表。为了验证细胞摄取机制可能涉及响应膜电位跨生物膜分布的假设，我们在培养的小鼠BALB/c 3T3、NIH 3T3和v-src转化的NIH 3T3成纤维细胞以及培养的鸡胚心脏细胞中测定了Tc-MIBI的净摄取和保留。用130 mM k20 mM Cl缓冲液对质膜电位进行等体积去极化，降低了所有制剂中Tc-MIBI的净细胞摄取。在BALB/c 3T3细胞中，与高钾缓冲液中的缬霉素或与质子载体CCCP一起使用的去极化线粒体膜电位抑制了Tc-MIBI的净摄取和保留，而与K+/H+交换剂尼日利亚霉素一起使用的超极化线粒体和质膜电位增加了Tc-MIBI的净摄取。这些结果表明，Tc-MIBI在成纤维细胞中的净细胞摄取和保留是由线粒体和质膜电位决定的；因此，Tc-MIBI的伽马发射特性可能会提高在体内监测膜电位的可能性。
Hexakis(2-methoxyisobutylisonitrile) technetium(I) (Tc-MIBI) is representative of a class of 99mTc-based lipophilic cationic myocardial perfusion imaging agents. To test the hypothesis that the mechanism of cellular uptake may involve distribution across biologic membranes in response to membrane potential, Tc-MIBI net uptake and retention were determined in cultured mouse BALB/c 3T3, NIH 3T3, and v-src transformed NIH 3T3 fibroblasts as well as in cultured chick embryo heart cells. Isovolumic depolarization of plasma membrane potentials with 130 mM K 20 mM Cl buffer decreased Tc-MIBI net cell uptake in all preparations. In BALB/c 3T3 cells, depolarizing mitochondrial membrane potential with valinomycin in high K buffer or with the protonophore CCCP inhibited net uptake and retention of Tc-MIBI while hyperpolarizing mitochondrial and plasma membrane potentials with the K+/H+ exchanger nigericin increased Tc-MIBI net uptake. These results indicated that net cellular uptake and retention of Tc-MIBI in fibroblasts were determined by both mitochondrial and plasma membrane potentials; the gamma-emitting properties of Tc-MIBI may therefore raise the possibility of monitoring membrane potential in vivo.