title: Transmembrane ICa contributes to rate-dependent changes of action potentials in human ventricular myocytes.
abstract: The mechanism of action potential abbreviation caused by increasing rate in human ventricular myocytes is unknown. The present study was designed to determine the potential role of Ca2+ current (ICa) in the rate-dependent changes in action potential duration (APD) in human ventricular cells. Myocytes isolated from the right ventricle of explanted human hearts were studied at 36 degreesC 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 decreased rate-dependent changes in APD (to 6 +/- 3%, P < 0.01). Peak ICa was decreased by 34 +/- 3% from 0.5 to 2 Hz (P < 0.01), and ICa had recovery time constants of 65 +/- 12 and 683 +/- 39 ms at -80 mV. Action potential clamp demonstrated a decreasing contribution of ICa during the action potential as rate increased. The rate-dependent slow component of the delayed rectifier K+ current (IKs) was not observed in four cells with an increase in frequency from 0.5 to 3.3 Hz, perhaps because the IKs is so small that the increase at a high rate could not be seen. These results suggest that reduction of Ca2+ influx during the action potential accounts for most of the rate-dependent abbreviation of human ventricular APD.
authors.affiliation: Department of Medicine, Montreal, Quebec, Canada H1T 1C8.
authors.forename: G R
authors.initials: GR
authors.lastname: Li
authors.forename: B
authors.initials: B
authors.lastname: Yang
authors.forename: J
authors.initials: J
authors.lastname: Feng
authors.forename: R F
authors.initials: RF
authors.lastname: Bosch
authors.forename: M
authors.initials: M
authors.lastname: Carrier
authors.forename: S
authors.initials: S
authors.lastname: Nattel
mesh_terms: D000200:Action Potentials / Q000502:physiology; D002118:Calcium / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D004553:Electric Conductivity; D006801:Humans; D009206:Myocardium / Q000166:cytology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000502:physiology; D011930:Reaction Time / Q000502:physiology; D016276:Ventricular Function / Q000502:physiology*
chemical_list: D011188:Potassium; D002118:Calcium