And the correct answer is cumulative inactivation of the sodium current. So what are the observations? The observations are at increasing pacing rate, there's slowing of conduction velocity at the fastest rates, and shortening of the action potential duration. So increasing rate will reduce action potential duration and refractory periods in several ways. In intact animals and humans, sympathetic activation with increased heart rate is likely to be involved, but not so in this culture system, and is less likely to slow conduction velocity. Cumulative inactivation of a repolarizing potassium current like IKS will hasten repolarization and shorten phase three of the action potential duration, not prolong it, but inactivation will prolong the APD and not affect conduction velocity. Increasing rate in a normal heart cell will increase, not deplete, SR calcium load and enhance calcium dependent inactivation of L-type calcium current may contribute to action potential duration shortening, which is actually required with increasing heart rate. Increasing rate can, although, lead to cumulative inactivation of sodium current, which would tend to slow conduction at excessively fast rates. Think of, you know, rate-related bundle branch blocks, and inactivation of any late component would tend to shorten the action potential duration. So again, the best answer here is cumulative inactivation of the sodium current.

conduction velocity

action potential duration

calcium handling

sodium current

pacing rate