Electrophysiological Mechanisms and Therapeutic Potential of Calcium Channels in Atrial Fibrillation

Figures

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  Fig. 1.. Two cardiac rhythms. (A) The left electrocardiogram shows sinus rhythm. The sinoatrial (SA) node, located in the right atrium, can spontaneously generate action potentials. The electrical impulses generated by the SA node are rapidly propagated to both the left and right atria, and then transmitted to the ventricles via the atrioventricular (AV) node. The impulses then spread rapidly throughout the ventricles via the Purkinje fiber system, leading to synchronized contraction of the ventricular muscle and the expulsion of blood. (B) The right electrocardiogram shows atrial fibrillation (AF). AF is typically triggered by spontaneous firing from ectopic pacemaker sites, with the most common trigger originating from the pulmonary veins. These ectopic pacemaker sites are influenced by various factors, which promote the initiation and maintenance of AF. Electrical impulses continuously circulate within the atria, resulting in rapid and irregular electrical activity. AF can lead to various complications. Fig. 1 was drawn using BioRender.

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  Fig. 2.. The mechanism of calcium channels regulating Ca2+ in cardiomyocytes. GPCR regulates the level of intracellular and extracellular Ca2+ by activating G protein; calcium channels distributed in cell membranes and organelles regulate the balance of Ca2+. The binding of Stromal Interaction Molecule 1 (STIM1) on the sarcoplasmic reticulum (SR) with Orai Calcium Release-Activated Calcium Modulator 1 (ORAI1) on the cell membrane participates in the regulation of calcium ions. The red and green arrows indicate the directions of Ca2+ and Na⁺ movement, respectively. LTCC, L-type calcium channel; RyR2, ryanodine receptor 2; TRP channel, transient receptor potential channel; NCX, sodium-calcium exchanger; IP3R, inositol 1,4,5-triphosphate receptor; SERCA, sarcoplasmic/endoplasmic reticulum Ca2+-ATPase; PLB, phospholamban; ATP, adenosine triphosphate; P, phosphate; GPCR, G-Protein coupled receptor; Ror, receptor tyrosine kinase-like orphan receptor; Wnt5a, wnt family member 5A; FZD6, frizzled class receptor 6; PLC, phospholipase C; PIP2, phosphatidylinositol 4,5-bisphosphate; IP3, inositol trisphosphate; DAG, diacylglycerol; PKC, protein kinase C. Fig. 2 was drawn using BioRender.

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  Fig. 3.. Factors regulating calcium channels in cardiomyocytes. The octagon represents different stimulating factors, and the arrow points to the calcium channel regulated by this factor. ROS, reactive oxygen species; PKA, protein kinase A; cAMP, cyclic adenosine monophosphate; CaMKII, calcium/calmodulin-dependent protein kinase II; CaM, calmodulin; P2YR, purinergic receptor P2Y; GPCR, G-protein coupled receptor. Fig. 3 was drawn using BioRender.