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Lithium ion as a probe of Na + channel activity in isolated rat hearts: a multinuclear NMR study
Author(s) -
Kupriyanov V. V.,
Xiang B.,
Yang L.,
Deslauriers R.
Publication year - 1997
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/(sici)1099-1492(199709)10:6<271::aid-nbm473>3.0.co;2-l
Subject(s) - chemistry , veratridine , bumetanide , extracellular , sodium , ion transporter , sodium channel , ion , biochemistry , organic chemistry
The aim of this study was to analyze Na + fluxes in whole perfused hearts using Li + as a Na + congener and 7 Li‐nuclear 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 + 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 μM) 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 μM, 0.057±0.006). Dimethylamiloride did not affect k (10 μM, 0.024±0.006) in Lidocaine‐arrested hearts. Bumetanide (30 μM, 0.094±0.013), nifedepine (0.33 μM, 0.088±0.009), Bay K8644 (0.1 μM, 0.080±0.002), 4‐aminopyridine (1.5 mM, 0.076±0.006) and cromakalim (10 μM, 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. © 1997 John Wiley & Sons, Ltd.