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Direct measurement of increased myocardial cellular23Na NMR signals in perfused guinea-pig heart induced by dihydroouabain and grayanotoxin-I

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Abstract

The effects of the cardiac glycoside dihydroouabain (DHO), and the ericaceous toxin grayanotoxin-I (GTX-I) on myocardial cellular sodium (Nai) concentrations were investigated using sodium-23 nuclear magnetic resonance (23Na NMR) spectroscopy at 30°C in isolated perfused guinea-pig hearts. The Nai NMR signals from perfused Langendorff heart preparations were obtained by the modified inversion recovery (IR) method based on the previous observation that the spin-lattice relaxation time (T1) of the Nai (25 or 34 msec at 8.46 Tesla (T)) is much faster than that of extracellular sodium (64 msec at 9.4 T). Nai was estimated from the calibration curve of the frequency area of the23Na NMR FT spectra plotted against the standard Na concentration. The Nai concentration of the heart increased concomitantly with the positive inotropic effects (PIE) of DHO, GTX-I and monensin (MON). The cumulative sequential addition of DHO (5×10−6 M), GTX-I (7×10−8 M) and MON (5×10−6 M), each of which alone induced no appreciable PIE, produced a 22% elevation in Nai concentration relative to that of the control (100%) accompanying a PIE of 44%. The mechanism of this Nai elevation induced by combinational addition of DHO, GTX-I and MON may be mediated as follows: GTX-I increases the net Na-influxvia Na+ channels; DHO inhibits the pumping out of Na+ from the cell; and MON transports external Na+ into the cell, acting as a sodium ionophore. Consequently, these drugs act synergistically to increase the Nai, thereby increasing the intracellular Ca2+ concentrationvia Na+−Ca2+ exchange.

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Authors and Affiliations

  1. Department of Pharmacology, Aichi Medical University, 21 Yazako-aza-Karimata Nagakute, 480-11, Aichi, Japan

    Yoshihiro Hotta, Hiroaki Ando & Kazumi Takeya

  2. Faculty of Pharmaceutical Sciences, Nagoya City University, Tanabe-dori, Mizuho-ku, 467, Nagoya, Japan

    Jinsaku Sakakibara

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  1. Yoshihiro Hotta
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  2. Hiroaki Ando
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  3. Kazumi Takeya
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  4. Jinsaku Sakakibara
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Hotta, Y., Ando, H., Takeya, K. et al. Direct measurement of increased myocardial cellular23Na NMR signals in perfused guinea-pig heart induced by dihydroouabain and grayanotoxin-I. Mol Cell Biochem 139, 59–70 (1994). https://doi.org/10.1007/BF00944204

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  • DOI: https://doi.org/10.1007/BF00944204

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