Referenced in: none

Automatically associated channels: Kv4.1 , Slo1

Title: Action potential duration restitution and alternans in rabbit ventricular myocytes: the key role of intracellular calcium cycling.

Authors: Joshua I Goldhaber, Lai-Hua Xie, Tan Duong, Christi Motter, Kien Khuu, James N Weiss

Journal, date & volume: Circ. Res., 2005 Mar 4 , 96, 459-66

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/15662034

Abstract
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 36 degrees C, 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.