Rate-force relationship and calcium overload in canine Purkinje fibers

The relationship between driving rate and contractile force was studied in calcium-overloaded canine cardiac Purkinje fibers perfused in vitro. The following results were obtained. In Tyrode solution (2.7 mM Ca), increasing the drive rate ('overdrive') induced an initial decrease followed by a progressive increase in force; the initial decrease was more pronounced and the subsequent increase slower when the driving rate was faster; returning to the basal slow rate caused a transient increase in force above control and this increase was greater when overdrive was faster; a stepwise increase and decrease in rate led to an initial decrease in force with each increment in rate and an initial increase with each decrement in rate; increasing [Ca]o up to 16.2 mM reversed both the initial fall during and the transient increase in force after overdrive; these changes in force were associated with oscillatory potentials, a sign of calcium overload; similar results were obtained by inducing calcium overload with a low [Na]o solution or strophanthidin; the altered force patterns and the oscillatory potentials were reduced or eliminated if calcium load was reduced by decreasing the basal rate or [Ca]o, by increasing [K]o or by administering tetrodotoxin. It is concluded that in Purkinje fibers the force-frequency relationship is markedly altered in the presence of calcium overload because overdrive further increases the calcium load and this results in a reversal of the relation between calcium and force.