Triggered Ca 2+ Waves Induce Depolarization of Maximum Diastolic Potential and Action Potential Prolongation in Dog Atrial Myocytes

Circ Arrhythm Electrophysiol. 2020 Jun;13(6):e008179. doi: 10.1161/CIRCEP.119.008179. Epub 2020 May 20.

Abstract

Background: We have identified a novel form of abnormal Ca2+ wave activity in normal and failing dog atrial myocytes which occurs during the action potential (AP) and is absent during diastole. The goal of this study was to determine if triggered Ca2+ waves affect cellular electrophysiological properties.

Methods: Simultaneous recordings of intracellular Ca2+ and APs allowed measurements of maximum diastolic potential and AP duration during triggered calcium waves (TCWs) in isolated dog atrial myocytes. Computer simulations then explored electrophysiological behavior arising from TCWs at the tissue scale.

Results: At 3.3 to 5 Hz, TCWs occurred during the AP and often outlasted several AP cycles. Maximum diastolic potential was reduced, and AP duration was significantly prolonged during TCWs. All electrophysiological responses to TCWs were abolished by SEA0400 and ORM10103, indicating that Na-Ca exchange current caused depolarization. The time constant of recovery from inactivation of Ca2+ current was 40 to 70 ms in atrial myocytes (depending on holding potential) so this current could be responsible for AP activation during depolarization induced by TCWs. Modeling studies demonstrated that the characteristic properties of TCWs are potentially arrhythmogenic by promoting both conduction block and reentry arising from the depolarization induced by TCWs.

Conclusions: Triggered Ca2+ waves activate inward NCX and dramatically reduce atrial maximum diastolic potential and prolong AP duration, establishing the substrate for reentry which could contribute to the initiation and maintenance of atrial arrhythmias.

Keywords: action potential; atrial fibrillation; calcium channel; computer simulation; diastole.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Action Potentials*
  • Animals
  • Arrhythmias, Cardiac / metabolism*
  • Arrhythmias, Cardiac / physiopathology
  • Calcium Signaling*
  • Computer Simulation
  • Diastole
  • Dogs
  • Female
  • Heart Rate*
  • Male
  • Models, Cardiovascular
  • Myocytes, Cardiac / metabolism*
  • Sodium-Calcium Exchanger / metabolism*
  • Time Factors

Substances

  • Sodium-Calcium Exchanger