The effects of hypertonicity on tension and intracellular calcium concentration in ferret ventricular muscle.

1. Tension and intracellular calcium concentration ([Ca2+]i) were measured in isolated ferret papillary muscles exposed to hypertonic solutions. [Ca2+]i was measured with aequorin which was microinjected into surface cells of the preparation. Correction was made for the effects of ionic strength on aequorin sensitivity to Ca2+. 2. Application of 100 mM-mannitol increased both developed tension and the intracellular Ca2+ signals on contraction (the Ca2+ transients). 300 mM-mannitol increased the Ca2+ transients further but led to a decrease in developed tension. 3. Mannitol caused a concentration-dependent slowing in the time course of a stimulated contraction but had no effect on that of the Ca2+ transient. 4. As the mannitol concentration was increased, the muscles exhibited increased viscosity which was demonstrated by measuring the tension response to a sudden stretch during diastole. This is probably a consequence of cell shrinkage and may cause the slower time course of the contraction. 5. In the presence of 300 mM-mannitol, oscillations of diastolic [Ca2+]i were detectable in both stimulated and quiescent preparations. However, in stimulated preparations the oscillations in mannitol were smaller than when a Ca2+ transient of similar amplitude was achieved by other means. 6. Immediately after the application or removal of mannitol large spontaneous Ca2+ signals were often observed. These signals were even larger in Na+-free solutions, suggesting that they cannot be attributed to Na+-Ca2+ exchange. 7. The increase in developed tension in 100 mM-mannitol can be accounted for by the increased Ca2+ transients in combination with the inhibitory effects of ionic strength on myofibrillar tension production (Kentish, 1984). The decrease in developed tension at 300 mM-mannitol is dominated by the inhibitory effect of increased ionic strength on maximum Ca2+-activated tension.