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1 Department of Pharmacology, University of Mississippi Medical Center, Jackson, Mississippi
The effects of 10-6 M ouabain on contractile strength and calcium exchange in isolated rabbit left atria were investigated as a function of the number of contractions during a 5-minute exposure to Ca45.
As the number of beats was increased in control atria, the specific activity of the tissue increased to reach a maximum value between 300 and 500 beats. This is consistent with the existence of a contraction-dependent "pool" of calcium. The size of this "pool" was estimated as being of the order of 10-6 to 10-7 moles Ca/kg wet tissue. The action of ouabain was associated with a marked increase in the maximum specific activity value. This result cannot be explained simply on the basis of an increased rate of exchange but suggests that ouabain has made more calcium available for contraction, perhaps by increasing the magnitude of the contraction-dependent pool.
It was demonstrated that during the early phase of ouabain toxicity, there is an additional 2-fold increase in specific activity. The effects of ouabain on calcium exchange may therefore be considered to proceed in two phases. The positive inotropic effect is associated with an increase in exchangeable calcium. Progression of the ouabain action to toxicity is associated with a further increase in calcium available for exchange, which may be a reflection of a slight increase in tissue calcium.
The uptake of calcium per beat in the presence and absence of ouabain was presented. After 10 beats had occurred, ouabain increased the uptake from 5.43 to 14.31 picomoles/cm2/ beat, a nearly 3-fold increase.
The question of whether ouabain alters calcium exchange and thereby affects contraction, or whether calcium exchange is altered as a result of changes in contractile force produced by some other action of ouabain, was considered. The data presented are interpreted as indicating that ouabain primarily affects calcium exchange and thereby affects the contractile force.
Accepted on January 19, 1965