Action potential duration restitution and alternans in rabbit ventricular myocytes - The key role of intracellular calcium cycling

作者：Goldhaber JI^*; Xie LH; Duong T; Motter C; Khuu K; Weiss JN

来源：Circulation Research, 2005, 96(4): 459-466.

DOI：10.1161/01.RES.0000156891.66893.83

• alternans
• arrhythmia
• Ca2+ transients
• action potential restitution

Action potential duration (APD) restitution properties and repolarization alternans are thought to be important arrhythmogenic factors. We investigated the role of intracellular calcium (Ca2+ (i)) cycling in regulating APD restitution slope and repolarization (APD) alternans in patch-clamped rabbit ventricular myocytes at 34 to 36degreesC, using the perforated or ruptured patch clamp techniques with Fura-2-AM to record Ca2+ (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 Ca2+ (i) accumulation during dynamic pacing. The onset of APD alternans occurred at diastolic intervals at which the APD restitution slope was significantly <1 and was abolished by suppressing sarcoplasmic reticulum (SR) Ca2+ (i) cycling with thapsigargin and ryanodine, or buffering the global Ca2+ (i) transient with BAPTA-AM or BAPTA. Thapsigargin and ryanodine flattened APD restitution slope to <1 when measured by the dynamic method, but not by the S1S2 method. BAPTA- AM or BAPTA failed to flatten APD restitution slope to <1 by either method. In conclusion, APD alternans requires intact Ca2+ (i) cycling and is not reliably predicted by APD restitution slope when Ca2+ (i) cycling is suppressed. Ca2+ (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 Ca2+ (i) accumulation.

• 出版日期2005-3-4