Electrophysiological Effects of Triggered Calcium Waves on the Action Potential in Left Atrial Myocytes from Normal and Failing Dog Heart

Abstract

We previously reported that triggered Ca waves (TCWs) occur in dog atrial myocytes during rapid pacing. The goal of this study was to investigate the effect of TCWs on APs during rapid pacing in left atrial myocytes from both normal and failing hearts (rapid RV pacing model). Intracellular Ca and AP recordings were made in atrial myocytes isolated from normal and failing (HF) dog hearts loaded with Ca-sensitive fluorescent dyes and stimulated at increasingly rapid rates (1-5Hz). Both normal and HF atrial myocytes developed TCWs which increased action potential duration (APD) and reduced maximum diastolic potential (MDP) throughout the duration of each TCW. Depending on the timing of the TCW, both MDP and APD could be affected during a single or multiple cycles. TCWs developed at slower rates in HF than in normals so changes in AP and MDP also occurred at slower rates making TCWs of potentially greater importance to arrhythmogenesis in HF. A subset of TCWs failed to propagate along the cell length but were short enough to occur during only 1-2 APs. These events (triggered Ca flares, TCFs) produce the same overall electrophysiological effects as TCWs that propagate along the cell length. In summary, TCFs and TCWs cause APD prolongation and cell depolarization in normal and diseased atrial myocytes probably by inducing inward Na+-Ca2+ exchange current in response to these Ca release events. This depolarization and slowing of repolarization is likely to establish repolarization gradients and cause reentry thus promoting atrial arrhythmogenesis such as atrial fibrillation.