High Frequency–Induced Upregulation of Human Cardiac Calcium Currents

Background In mammalian heart cells, Ca2+ influx through voltage-gated L-type Ca2+ channels can be upregulated by high rates of stimulation. We have investigated this important adaptive regulation in human cardiomyocytes. Methods and Results Using the whole-cell patch-clamp technique, we found a high frequency–induced upregulation (HFIUR) of the dihydropyridine-sensitive L-type Ca2+ current (ICa) in human cardiomyocytes. ICa was potentiated in a graded manner with increasing rates of stimulation between 0.3 and 5 Hz. Both moderate increase of ICa peak amplitude and marked slowing of current decay contributed to large increases of Ca2+ influx (up to 80%). The maximal potentiation of ICa was reached rapidly after the change in the rate of stimulation (no more than a few seconds). β-Adrenergic stimulation of the cells by isoproterenol (1 μmol/L), which is well known to induce a slow (≈1 minute) cAMP-mediated potentiation of ICa, could enhance (when present) or promote (when absent) the HFIUR of ICa. As a con...