THE EFFECTS OF FREQUENCY OF STIMULATION AND CALCIUM CONCENTRATION ON Ca⁴⁵ EXCHANGE AND CONTRACTILITY ON THE ISOLATED GUINEA-PIG AURICLE

¹ Department of Pharmacology, State University of New York Downstate Medical Center, Brooklyn, New York

The uptake of Ca⁴⁵ into isolated guinea-pig left auricles takes place in at least two phases. The initial rapid phase of exchange appears to be complete in about 5 minutes. Comparison of uptake curves at various frequencies indicates that the extent of uptake during initial phase of exchange is dependent on the frequency of contraction. The slower phase of Ca⁴⁵ exchange appears to be similar in stimulated as well as resting muscles indicating that this latter phase of exchange is independent of contraction. Comparison of auricles stimulated under isotonic and isometric conditions indicated no significant difference in Ca⁴⁵ exchange between auricles allowed to shorten and those restricted mainly to the development of tension. It seems likely, therefore, that the increase in Ca⁴⁵ exchange in beating auricles during the initial phase is involved in the contractile process rather than being a secondary effect of the mechanical movements of the tissue.

It has been demonstrated that associated with increases in frequency there is an increase in Ca⁴⁵ exchange as well as an increase in contractile amplitude. At an external calcium concentration of 2.32 mM, Ca⁴⁵ exchange during a 5-minute incubation increases with frequency up to 30 beats/minute; however, the relationship between increase in exchange and increase in contractility is not a direct one. Beyond this frequency relatively little or no increase in Ca⁴⁵ exchange could be demonstrated. However, contractility at the higher frequencies (60 and 120 beats/min) continues to rise despite no apparent increase in Ca⁴⁵ exchange. The data have been interpreted to indicate that a calcium "pool" exists which exchanges sufficiently rapidly with extracellular calcium at frequencies of 30 beats/minute or higher, to attain essentially the specific activity of the latter (pool saturation). Although the entire pool may become exchangeable at frequencies in the range of 30 beats/minute or higher, increases in contractility with frequency in this range are also believed to be associated with increases in the extent of calcium exchange per beat.

When the frequency of contraction was varied at lower calcium concentrations (0.51 and 1.06 mM), the pool saturation phenomenon was not observed at any frequency tested (up to 120 beats/min) during a 5-minute incubation with Ca⁴⁵. Also, there seemed to be a more direct correlation between contractility and Ca⁴⁵ exchange at these lower calcium concentrations than at the normal concentration (2.32 mM). Since there was some positive relationship between Ca⁴⁵ exchange and contractility at all calcium concentrations employed, it is concluded that calcium is intimately involved in the phenomenon of increase in contractile strength with ncrease in frequency.

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