Rate dependence and supernormality in excitability of guinea pig papillary muscle

It is well known that in most cardiac tissues an increase in rate results in a decrease of excitability and, eventually, conduction block. We used microelectrode techniques to evaluate the rate and time dependence of excitation latency in 27 isolated guinea pig papillary muscles (GPPM). Latency was measured as the interval between the stimulus onset and action potential upstroke. When the intensity of current was just suprathreshold, prolongation of the basic cycle length (BCL) from 300 to 1,000 ms produced an increase in latency or failure of excitation. Such behavior was observed with extracellular as well as intracellular stimulation. Rate-dependent changes in latency were maximal during the first 10-20 s following the rate change and reached a steady state in approximately 200 s. Application of premature beats revealed the presence of a "supernormal phase" in which latency abbreviated. Strength-interval and strength-duration curves demonstrated that changes in excitability accurately paralleled those observed in latency. Hence, supernormal excitability at the end of the phase 3 repolarization was consistently observed in all ventricular muscle experiments. Deceleration-induced decrease of excitability was attended by hyperpolarization, increase of action potential upstroke velocity (Vmax) and action potential amplitude, and decrease in membrane resistance. Our data suggest that paradoxical rate-related changes of excitability in GPPM are the result of changes in the passive membrane properties. Under conditions of depressed conductivity, this particular behavior may account for the occurrence of bradycardia-dependent block.