Differences in rate dependence of transient outward current in rabbit and human atrium

Both human and rabbit atrial cells possess a large 4-aminopyridine-sensitive transient outward current (I(to1)). However, the slow reactivation of this current in rabbits suggests that its role may be limited to very slow heart rates. We used whole cell voltage-clamp recordings to evaluate the rate dependency of I(to1) in rabbit and human atrial myocytes. Our results show that at physiological temperatures in human atrium, I(to1) is rate independent at rates between 0.1 and 4.0 Hz. Peak I(to1) at 4.0 Hz in rabbit was 3.4 +/- 1.4% (mean +/- SE) of current at 0.1 Hz (P < 0.001, n = 8), whereas in humans, peak I(to1) at 4.0 Hz averaged 88.8 +/- 6.1% of the current at 0.1 Hz (P > 0.05, n = 7). These differences were due to marked discrepancies in reactivation time course, which was biexponential with time constants that averaged 650 +/- 159 ms and 8.4 +/- 1.1 s in rabbit (n = 8) compared with a single exponential time constant of 33.6 +/- 6.8 ms (n = 8) in human atrium (both at 30 degrees C). These findings suggest that I(to1) can contribute importantly to atrial repolarization at all physiological heart rates in humans. Furthermore, these results emphasize that there are important interspecies variations in the rate dependence of I(to1), which need to be considered in understanding the physiological and pharmacological regulation of atrial repolarization.