Action Potential Duration Restitution and Alternans in Rabbit Ventricular Myocytes

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Abstract
Action potential duration (APD) restitution properties and repolarization alternans are thought to be important arrhythmogenic factors. We investigated the role of intracellular calcium (Ca 2+ i ) cycling in regulating APD restitution slope and repolarization (APD) alternans in patch-clamped rabbit ventricular myocytes at 34 to 36°C, using the perforated or ruptured patch clamp techniques with Fura-2-AM to record Ca 2+ i . When APD restitution was measured by either the standard extrastimulus (S1S2) method or the dynamic rapid pacing method, the maximum APD restitution slope exceeded 1 by both methods, but was more shallow with the dynamic method. These differences were associated with greater Ca 2+ i accumulation during dynamic pacing. The onset of APD alternans occurred at diastolic intervals at which the APD restitution slope was significantly 2+ i cycling with thapsigargin and ryanodine, or buffering the global Ca 2+ i transient with BAPTA-AM or BAPTA. Thapsigargin and ryanodine flattened APD restitution slope to 2+ i cycling and is not reliably predicted by APD restitution slope when Ca 2+ i cycling is suppressed. Ca 2+ i cycling may contribute to differences between APD restitution curves measured by S1S2 versus dynamic pacing protocols by inducing short-term memory effects related to pacing-dependent Ca 2+ i accumulation.