锂离子作为离体大鼠心脏中钠离子通道活性的探针：一项多核核磁共振研究。
Lithium ion as a probe of Na+ channel activity in isolated rat hearts: a multinuclear NMR study.
作者信息
Kupriyanov V V, Xiang B, Yang L, Deslauriers R
机构信息
Institute for Biodiagnostics, National Research Council Canada, Winnipeg, MB, Canada.
出版信息
NMR Biomed. 1997 Sep;10(6):271-6. doi: 10.1002/(sici)1099-1492(199709)10:6<271::aid-nbm473>3.0.co;2-l.
The aim of this study was to analyze Na+ fluxes in whole perfused hearts using Li+ as a Na+ congener and 7Li-nuclear magnetic resonance as a detection method. Hearts were equilibrated for 32 min with 15 mM LiCl added to P1-free Krebs-Henseleit buffer (intracellular space (ICS) [Li+] = 21.5 +/- 3.4 mM). Li+ efflux was monitored using a Li(+)-free perfusate. The effects of drugs on Li+ efflux were studied by adding the compounds 4 min prior to initiating Li+ washout. 7Li-NMR spectra were collected every 2 min at 139.95 MHz. Li+ efflux was biphasic with rate constants (k +/- SD, min-1) of 0.5 +/- 0.1 (extracellular) and 0.09 +/- 0.01 (ICS). Li+ efflux from ICS was dependent on heart rate (HR): cardiac arrest produced by 1 mM lidocaine or 20 mM KCl reduced k to 1/3 of its control value (Lidocaine, 0.030 +/- 0.004; KCl, 0.035 +/- 0.003). Increasing concentrations of carbachol (0.2-3.0 microM) caused a gradual decrease in HR and revealed a linear relationship between k and HR. In KCl-arrested hearts the Na+ channel opener veratridine increased k by 60% (10 microM, 0.057 +/- 0.006). Dimethylamiloride did not affect k (10 microM, 0.024 +/- 0.006) in Lidocaine-arrested hearts. Bumetanide (30 microM, 0.094 +/- 0.013), nifedepine (0.33 microM, 0.088 +/- 0.009), Bay K8644 (0.1 microM, 0.080 +/- 0.002), 4-aminopyridine (1.5 mM, 0.076 +/- 0.006) and cromakalim (10 microM, 0.088 +/- 0.006) did not significantly affect either k or HR. Li+ efflux from myocytes in perfused rat heart is mediated mainly by voltage-dependent Na+ channels.
本研究的目的是使用锂离子（Li⁺）作为钠离子（Na⁺）的同类物，并采用⁷Li-核磁共振作为检测方法，分析全灌注心脏中的Na⁺通量。向无P1的克雷布斯-亨泽莱特缓冲液中添加15 mM LiCl，使心脏平衡32分钟（细胞内空间（ICS）[Li⁺]=21.5±3.4 mM）。使用无Li⁺的灌注液监测Li⁺流出。在开始Li⁺洗脱前4分钟加入化合物，研究药物对Li⁺流出的影响。每2分钟在139.95 MHz采集⁷Li-NMR光谱。Li⁺流出呈双相性，速率常数（k±SD，min⁻¹）分别为0.5±0.1（细胞外）和0.09±0.01（ICS）。ICS中的Li⁺流出取决于心率（HR）：1 mM利多卡因或20 mM KCl导致的心脏停搏使k降至其对照值的1/3（利多卡因，0.030±0.004；KCl，0.035±0.003）。增加卡巴胆碱浓度（0.2 - 3.0 microM）导致HR逐渐降低，并揭示了k与HR之间的线性关系。在KCl停搏的心脏中，Na⁺通道开放剂藜芦碱使k增加60%（10 microM，0.057±0.006）。在利多卡因停搏的心脏中，二甲基amiloride不影响k（10 microM，0.024±0.006）。布美他尼（30 microM，0.094±0.013）、硝苯地平（0.33 microM，0.088±0.009）、Bay K8644（0.1 microM，0.080±0.002）、4-氨基吡啶（1.5 mM，0.076±0.006）和克罗卡林（10 microM，0.088±0.006）对k或HR均无显著影响。灌注大鼠心脏中肌细胞的Li⁺流出主要由电压依赖性Na⁺通道介导。
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