The Calcium Transient Coupled to the L-Type Calcium Current Attenuates Action Potential Alternans.

Background: Action potential (AP) alternans are linked to increased arrhythmogenesis. It is suggested that calcium (Ca Methods: AP (patch clamp) and intracellular Ca Results: After a rate change, alternans were critically damped and stable, overdamped and ceased over seconds, underdamped with longer scale harmonics, or unstably underdamped progressing to 2:1 capture. Alternans in control cells were predominantly critically damped, but after CaT ablation with 10 or 20 mM BAPTA, exhibited respectively increased overdamping or increased underdamping. Alternans were easier to induce in CaT free cells as evidenced by a higher alternans threshold (ALT-TH: at least 7 pairs of alternating beats) relative to control cells. Alternans in Bay K 8644 treated cells were often underdamped, but the ALT-TH was similar to control. In CaT ablated cells, Bay K 8644 prolonged AP duration (APD) leading predominantly to unstably underdamped alternans. Conclusions: AP alternans occur more readily in the absence of CaT suggesting that the CaT dampens the development of AP alternans. The data further demonstrate that agonizing the L-type calcium current without the negative feedback of the CaT leads to unstable alternans. This negative feedback mechanism may be important for understanding treatments aimed at reducing CaT or its dynamic response to prevent arrhythmias.