کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5533693 | 1550401 | 2017 | 10 صفحه PDF | دانلود رایگان |

- Atrial Ca2Â + alternans coincide with action potential (AP) alternans.
- Development and degree of Ca2Â + alternans are modulated by AP morphology.
- AP alternans leads to alternans in sarcoplasmic reticulum Ca2Â + ([Ca2Â +]SR).
- L-type Ca2Â + current is significantly affected by alternations in AP morphology.
- Thus, AP alternans shapes Ca2Â + alternans via Ca2Â + current and [Ca2Â +]SR modulation.
Alternans is a risk factor for cardiac arrhythmia, including atrial fibrillation. At the cellular level alternans is observed as beat-to-beat alternations in contraction, action potential (AP) morphology and magnitude of the Ca2Â + transient (CaT). It is widely accepted that the bi-directional interplay between membrane voltage and Ca2Â + is crucial for the development of alternans, however recently the attention has shifted to instabilities in cellular Ca2Â + handling, while the role of AP alternation remains poorly understood. This study provides new insights how beat- to-beat alternation in AP morphology affects occurrence of CaT alternans in atrial myocytes.Pacing-induced AP and CaT alternans were studied in rabbit atrial myocytes using combined Ca2Â + imaging and electrophysiological measurements. To determine the role of AP morphology for the generation of CaT alternans, trains of two voltage commands in form of APs recorded during large and small alternans CaTs were applied to voltage-clamped cells. APs of longer duration (as observed during small amplitude alternans CaT) and especially beat-to-beat alternations in AP morphology (AP alternans) reduced the pacing frequency threshold and increased the degree of CaT alternans. AP morphology contributes to the development of CaT alternans by two mechanisms. First, the AP waveform observed during small alternans CaTs coincided with higher end-diastolic sarcoplasmic reticulum Ca2Â + levels ([Ca2Â +]SR), and AP alternans resulted in beat-to-beat alternations in end-diastolic [Ca2Â +]SR. Second, L-type Ca2Â + current was significantly affected by AP morphology, where the AP waveform observed during large CaT elicited L-type Ca2Â + currents of higher magnitude and faster kinetics, resulting in more efficient triggering of SR Ca2Â + release.In conclusion, alternation in AP morphology plays a significant role in the development and stabilization of atrial alternans. The demonstration that CaT alternans can be controlled or even prevented by modulating AP morphology has important ramifications for arrhythmia prevention and therapy strategies.
Journal: Journal of Molecular and Cellular Cardiology - Volume 105, April 2017, Pages 49-58