Arrhythmogenic late Ca²⁺ sparks in failing heart cells and their control by action potential configuration.

ABSTRACT: Sudden death in heart failure patients is a major clinical problem worldwide, but it is unclear how arrhythmogenic early afterdepolarizations (EADs) are triggered in failing heart cells. To examine EAD initiation, high-sensitivity intracellular Ca²⁺ measurements were combined with action potential voltage clamp techniques in a physiologically relevant heart failure model. In failing cells, the loss of Ca²⁺ release synchrony at the start of the action potential leads to an increase in number of microscopic intracellular Ca²⁺ release events ("late" Ca²⁺ sparks) during phase 2-3 of the action potential. These late Ca²⁺ sparks prolong the Ca²⁺ transient that activates contraction and can trigger propagating microscopic Ca²⁺

SUBMITTER: Fowler ED 

PROVIDER: S-EPMC7007549 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature