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Restoration of osmotically inhibited twitch force in rat cardiac trabeculae: Role of Na+–H+ exchange

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Summary

1. When rat cardiac muscle is subjected to an increase of osmolality, its peak twitch force is immediately inhibited. Subsequently, over a period of several minutes, twitch force undergoes restoration, the extent of which is determined by the osmolality. The aim of the present study was to determine the factors that contribute to this restorative phenomenon.

2. Trabeculae were isolated from the right ventricles of rat hearts and mounted in an organ bath at 37°C. The osmolality of the bathing solution was increased by 100 mOsmol (to 400 mOsmol) by the addition of various proportions of NaCl and sucrose while recording twitch force production. The role of Na+–H+ exchange in restoring twitch force was examined by use of the specific inhibitor cariporide (HOE 642). The role of Na+–Ca2+ exchange was examined by reducing [Ca2+]o (from 2 mmol/L to 0.5 mmol/L) or by substituting LiCl for NaCl.

3. Cariporide (25 µmol/L) completely abolished twitch force restoration, thereby implicating a central role for the Na+–H+ exchanger. At constant [Na+]o, the extent of restoration was [Ca2+]o dependent, suggesting an independent contribution by the Na+–Ca2+ exchanger. This suggestion was supported by the finding that Li+, which substitutes for Na+ on the Na+–H+ exchanger, but not on the Na+–Ca2+ exchanger, also reduced the extent of restoration of hyperosmotically inhibited twitch force.

4. We conclude that the immediate inhibition of peak twitch force of rat cardiac muscle by hyperosmotic solutions reflects, in part, elevation of [H+]i, subsequent to reduction of cell volume. Hyperosmotic activation of Na+–H+ exchange then progressively relieves the inhibitory effect of protons on force development. The accompanying increase in [Na+]i in turn enhances Ca2+ influx on the Na+–Ca2+ exchanger, with the result that twitch force undergoes further restoration.
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Keywords: Na+–Ca2+ exchange; Na+–H+ exchange; hyperosmolarity; rat heart; trabeculae

Document Type: Research Article

Publication date: March 1, 2003

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