Disturbances in intracellular Ca(2+) signaling are the primary mechanism underlying alternans in atrial cells, with action potential duration alternans occurring as a secondary consequence.
RATIONALE: Alternans is a risk factor for cardiac arrhythmia, including atrial fibrillation. At the cellular level alternans manifests as beat-to-beat alternations in contraction, action potential duration (APD), and magnitude of the Ca(2+) transient (CaT). Electromechanical and CaT alternans are highly correlated, however, it has remained controversial whether the primary cause of alternans is a disturbance of cellular Ca(2+) signaling or electrical membrane properties. OBJECTIVE: To determine whether a primary failure of intracellular Ca(2+) regulation or disturbances in membrane potential and AP regulation are responsible for the occurrence of alternans in atrial myocytes. METHODS AND RESULTS: Pacing-induced APD and CaT alternans were studied in single rabbit atrial and ventricular myocytes using combined Ca(2+)i and electrophysiological measurements. In current-clamp experiments, APD and CaT alternans strongly correlated in time and magnitude. CaT alternans was observed without alternation in L-type Ca(2+) current, however, elimination of intracellular Ca(2+) release abolished APD alternans, indicating that Ca(2+)i dynamics have a profound effect on the occurrence of CaT alternans. Trains of 2 distinctive voltage commands in form of APs recorded during large and small alternans CaTs were applied to voltage-clamped cells. CaT alternans was observed with and without alternation in the voltage command shape. During alternans AP-clamp large CaTs coincided with both long and short AP waveforms, indicating that CaT alternans develop irrespective of AP dynamics. CONCLUSIONS: The primary mechanism underlying alternans in atrial cells, similarly to ventricular cells, resides in a disturbance of Ca(2+) signaling, whereas APD alternans are a secondary consequence, mediated by Ca(2+)-dependent AP modulation.
Kanaporis et al. (Tue,) conducted a other in Cardiac alternans. Pacing-induced APD and CaT alternans was evaluated on Mechanism of alternans (CaT vs APD). Disturbances in intracellular Ca(2+) signaling are the primary mechanism underlying alternans in atrial cells, with action potential duration alternans occurring as a secondary consequence.