Pathological NRSF-Gα o pathway in the progression of heart failure. (IMAGE)
Caption
Gα o gene expression is regulated by a transcriptional repressor NRSF. In pathological conditions of the heart, NRSF repressor function is attenuated through activation of CaMKII signaling pathway, thereby increasing Gα o expression. The resultant Gα o -mediated increases in the LTCC current density at the surface sarcolemma and the cytosolic Ca 2+ concentration lead to CaMKII activation, further suppressing NRSF- mediated repression. Gα o thus fulfills a positive CaMKII-NRSF transcriptional circuit, which evokes pathological cardiac remodeling. Activated CaMKII also phosphorylates RyR2 and impairs Ca 2+ homeostasis via abnormal Ca 2+ leak from SR, ultimately leading to cardiac dysfunction and ventricular arrhythmias.
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Copyright © 2021 Wolters Kluwer Health, Inc.
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