A model for cooperative gating of L-type Ca2+ channels and its effects on cardiac alternans dynamics.

作者: Daisuke Sato , Rose E. Dixon , Luis F. Santana , Manuel F. Navedo

DOI: 10.1371/JOURNAL.PCBI.1005906

关键词:

摘要: In ventricular myocytes, membrane depolarization during the action potential (AP) causes synchronous activation of multiple L-type CaV1.2 channels (LTCCs), which trigger release calcium (Ca2+) from sarcoplasmic reticulum (SR). This results in an increase intracellular Ca2+ (Cai) that initiates contraction. During pulsus alternans, cardiac contraction is unstable, going weak to strong successive beats despite a constant heart rate. These alternans can be caused by instability (Vm) due steep AP duration (APD) restitution (Vm-driven alternans), Cai cycling (Ca2+-driven or both, and may modulated functional coupling between clustered (e.g. cooperative gating). Here, mathematical analysis computational models were used determine how changes strength gating LTCCs impact voltage dynamics heart. We found increasing degree increases amplitude currents (ICaL) prolongs (APD). Increased known promote potentially arrhythmogenic substrate. addition, our shows makes on (Cai→Vm coupling) more positive destabilizes Vm-Cai for Vm-driven Cai-driven but not quasiperiodic oscillation. suggest have major excitation-contraction coupling, only prolonging APD, also altering Cai→Vm promoting arrhythmias.

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