Lithium ion as a probe of Na+ channel activity in isolated rat hearts: a multinuclear NMR study
✍ Scribed by V. V. Kupriyanov; B. Xiang; L. Yang; R. Deslauriers
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 162 KB
- Volume
- 10
- Category
- Article
- ISSN
- 0952-3480
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✦ Synopsis
The aim of this study was to analyze Na + fluxes in whole perfused hearts using Li + as a Na + congener and 7 Linuclear magnetic resonance as a detection method. Hearts were equilibrated for 32 min with 15 mM LiCl added to P 1 -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. 7 Li-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 M) 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 M, 0.057 ± 0.006). Dimethylamiloride did not affect k (10 M, 0.024 ± 0.006) in Lidocaine-arrested hearts. Bumetanide (30 M, 0.094 ± 0.013), nifedepine (0.33 M, 0.088 ± 0.009), Bay K8644 (0.1 M, 0.080 ± 0.002), 4-aminopyridine (1.5 mM, 0.076 ± 0.006) and cromakalim (10 M, 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.