© 1995 American Heart Association, Inc.
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Pathways of Rb+ Influx and Their Relation to Intracellular [Na+] in the Perfused Rat Heart
A 87Rb and 23Na NMR Study
From the Institute for Biodiagnostics, National Research Council, Winnipeg, Canada. National Research Council publication NRC 34759.
Correspondence to Dr Valerie V. Kupriyanov, Institute for Biodiagnostics, National Research Council of Canada, 435 Ellice Ave, Winnipeg, Manitoba, Canada R3B 1Y6. E-mail kupriyanov @ibd.lan.nrc.ca.
Abstract The aims of this study were to characterize the routes of influx of the K+ congener, Rb+, into cardiac cells in the perfused rat heart and to evaluate their links to the intracellular Na+ concentration ([Na+]i) using 87Rb and 23Na nuclear magnetic resonance (NMR) spectroscopy. The rate constant for Rb+ equilibration in the extracellular space was 8.5 times higher than that for the intracellular space. The sensitivity of the rate of Rb+ accumulation in the intracellular space of the perfused rat heart to the inhibitors of the K+ and Na+ transport systems has been analyzed. The Rb+ influx rates were measured in both beating and arrested hearts: both procaine (5 mmol/L) and lidocaine (1 mmol/L) halved the Rb+ influx rate. In procaine-arrested hearts, the Na+,K+-ATPase inhibitor ouabain (0.6 mmol/L) decreased Rb+ influx by 76±24% relative to that observed in untreated but arrested hearts. Rb+ uptake was insensitive to the K+ channel blocker 4-aminopyridine (1 mmol/L). The inhibitor of Na+/K+/2 Cl- cotransport bumetanide (30 µmol/L) decreased Rb+ uptake only slightly (by 9±8%). Rb+ uptake was dependent on [Na+]i: it increased by 58±34% when [Na+]i was increased with the Na+ ionophore monensin (1 µmol/L) and decreased by 48±9% when [Na+]i was decreased by the Na+ channel blockers procaine and lidocaine. Dimethylamiloride (15 to 20 µmol/L), an inhibitor of the Na+/H+ exchanger, slightly reduced [Na+]i and Rb+ entry into the cardiomyocytes (by 15±5%). 31P NMR spectroscopy was used to monitor the energetic state and intracellular pH (pHi) in a parallel series of hearts. Treatment of the hearts with lidocaine, 4-aminopyridine, dimethylamiloride, or bumetanide for 15 to 20 minutes at the same concentrations as used for the Rb+ and Na+ experiments did not markedly affect the levels of the phosphate metabolites or pHi. These data show that under normal physiological conditions, Rb+ influx occurs mainly through Na+,K+-ATPase; the contribution of the Na+/K+/2 Cl- cotransporter and K+ channels to Rb+ influx is small. The correlation between Rb+ influx and [Na+]i during infusion of drugs that affect [Na+]i indicates that, in rat hearts at 37°C, Rb+ influx can serve as a measure of Na+ influx. We estimate that, at normothermia, at least 50% of the Na+ entry into beating cardiac cells is provided by the Na+ channels, with only minor contributions (<15%) from the Na+/K+/2 Cl- cotransporter and the Na+/H+ exchanger.
Key Words: Rb+ uptake • intracellular Na+ • rat heart • Na+,K+-ATPase • Na+ and K+ transport inhibitors
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