Voltage and time dependence of restitution in heart

Between beats, cardiac muscle gradually recovers the ability to contract in response to a stimulus. We examined the time and voltage dependence of this "restitution" process using sheep cardiac Purkinje fibers that were voltage clamped by the two-micro-electrode technique. The rate and time course of restitution depended on the voltage and duration of preceding conditioning depolarizations. As the voltage of a conditioning depolarization was made less negative, the early rate of restitution increased, the process reached a greater peak value, and oscillations in the time course of restitution became more likely. When conditioning depolarizations were to voltages near or above the normal action potential plateau, increasing their duration had much the same effect as increasing voltage. However, with conditioning depolarizations to -40 or -50 mV, prolongation had little or no effect on the subsequent rate of restitution. The voltage during restitution affected both the time course and final extent of restitution. Steady-state restitution was an approximately sigmoid function of voltage. The early rate and peak value of restitution increased as the voltage during restitution was made more negative. Oscillations of restitution were dramatic at voltages between -70 and -50 mV. The behavior of restitution confirms that most of the calcium that activates contraction comes from intracellular stores. The complex time and voltage dependence of restitution suggests that the process reflects the time course of calcium reaccumulation in an internal store.