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Transmembrane ICa contributes to rate-dependent changes of action potentials in human ventricular myocytes
Insights
Increasing heart rate shortens action potential duration in human ventricular cells. This study shows that reduced calcium influx (ICa) is the primary cause of this rate-dependent effect, impacting cardiac electrophysiology.
Area of Science:
- Cardiology
- Electrophysiology
- Cell Physiology
Background:
- The mechanism behind action potential duration abbreviation at higher heart rates in human ventricular myocytes remains unclear.
- Understanding this phenomenon is crucial for comprehending cardiac function and dysfunction.
Purpose of the Study:
- To investigate the role of calcium current (ICa) in rate-dependent changes of action potential duration (APD) in human ventricular cells.
- To elucidate the electrophysiological mechanisms underlying cardiac rate adaptation.
Main Methods:
- Utilized whole-cell voltage and current-clamp techniques on isolated human ventricular myocytes.
- Measured action potential duration (APD) at 90% repolarization across varying frequencies (0.5 Hz to 2 Hz).
- Employed equimolar Mg2+ substitution for Ca2+ and action potential clamp to assess ICa contribution.
Main Results:
- Action potential duration (APD) decreased by 36% when frequency increased from 0.5 to 2 Hz.
- Substituting Mg2+ for Ca2+ significantly reduced rate-dependent APD changes.
- Peak calcium current (ICa) decreased by 34% with increased frequency, and its contribution diminished during the action potential.
Conclusions:
- Reduced calcium influx during the action potential is the main driver of rate-dependent APD abbreviation in human ventricular myocytes.
- This finding clarifies a key aspect of human cardiac electrophysiology and rate adaptation.
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.