Transmembrane I-Ca contributes to rate-dependent changes of action potentials in human ventricular myocytes

The mechanism of action potential abbreviation caused by increasing rate in human ventricular myocytes is unknown. The present study was designed to d etermine the potential role of Ca2+ current (I-Ca) in the rate-dependent ch anges in action potential duration (APD) in human ventricular cells. Myocyt es isolated from the right ventricle of explanted human hearts were studied at 36 degrees C with whole cell voltage and current-clamp techniques. APD at 90% repolarization decreased by 36 +/- 4% when frequency increased from 0.5 to 2 Hz. Equimolar substitution of Mg2+ for Ca2+ significantly decrease d rate-dependent changes in APD (to 6 +/- 3%, P < 0.01). Peak I-Ca was decr eased by 34 +/- 3% from 0.5 to 2 Hz (P < 0.01), and I-Ca had recovery time constants of 65 +/- 12 and 683 +/- 39 ms at -80 mV. Action potential clamp demonstrated a decreasing contribution of I-Ca during the action potential as rate increased. The rate-dependent slow component of the delayed rectifi er K+ current (I-Ks) was not observed in four cells with an increase in fre quency from 0.5 to 3.3 Hz, perhaps because the I-Ks is SO Small that the in crease at a high rate could not be seen. These results suggest that reducti on of Ca2+ influx during the action potential accounts for most of the rate -dependent abbreviation of human ventricular APD.