The Role of Local Ca2+ Release for Ca2+ Alternans and SR-Ca2+ Leak

Hammer, K; Maier, Lars S.

doi:10.1007/978-3-319-54579-0_15

Cited by 1 publication

(1 citation statement)

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“…Gap junctions (GJs) electrotonically couple neighboring cardiac myocytes to form a whole functional syncytium, allowing the propagation of excitation waves [27] and synchronized contraction of the myocardium. Altered function of GJ may affect not only the conduction velocity of electrical signals for the simultaneous excitation of the heart, but also the synchronization of neighboring cells, leading to enhanced spatial gradients [28], [29]. Experiments have shown that partially inhibiting the gap junctions increases the occurrence and intensity of Ca 2+ alternans, indicating a crucial relationship between the GJ function and the formation of Ca 2+ alternans [11].…”

Section: And Multicellularmentioning

confidence: 99%

Alternans in Mouse Atrial Cardiomyocytes: A Computational Study on the Influence of Cell-Cell Coupling and β-Adrenergic Stimulation

Zhang

Wang

et al. 2020

IEEE Access

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Cardiac alternans is a dynamical phenomenon in cardiomyocytes, which is linked to the genesis of cardiac mechanical dysfunction and lethal arrhythmias. The beat-to-beat alteration may occur in the amplitude of Ca 2+ transients (CaT) or the action potential duration (APD). Typically, APD alternans is a secondary consequence of the CaT alternans and the generation of CaT alternans is relevant to the imbalance of the sarcoplasmic reticulum (SR) Ca 2+ release and uptake. However, the effect of cell-cell coupling and β-adrenergic receptor (β-AdR) stimulation on the initiation and inhibition of CaT alternans is not fully understood. Here, we used a biophysically detailed mathematical model of the mouse atrial myocyte to study the mechanism underlying alternans and the effects of β-AdR stimulation. The cell exhibited obvious CaT alternans under fast pacing due to sarcolemmal Ca 2+ flux imbalance leaded SR Ca 2+ flux imbalance, while no noticeable APD alternans was seen. The β-AdR agonist isoproterenol (ISO) inhibited CaT alternans by its regulatory role on amplifying the L-type Ca 2+ current. On a one-dimensional strand, cell-cell coupling indirectly alleviated CaT alternans by affecting the overshoot and APD, reducing the triggered SR Ca 2+ release. Variation in the cell-cell coupling did not change the pattern of CaT alternans or interfere with the alternans inhibitory effect of β-AdR stimulation. Taken together, our results imply a potentially antiarrhythmic effect of β-AdR stimulation and shed new light on the mechanisms behind the cardiac alternans.

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