CASQ2 Dog

CASQ2 is a high-capacity, low-affinity calcium-binding protein that can bind between 18 to 50 calcium ions per molecule . It helps to hold calcium ions in the cisterna of the sarcoplasmic reticulum after muscle contraction, ensuring that the concentration of calcium in the sarcoplasmic reticulum remains significantly higher than in the cytosol . This storage capability is critical for the rapid release of calcium ions during muscle contraction, which is necessary for the heart to function effectively.

CASQ2 is predominantly found in cardiac muscle and slow-twitch skeletal muscle . It plays a pivotal role in regulating cardiac excitation-contraction coupling and calcium-induced calcium release (CICR) in the heart . Overexpression of CASQ2 has been shown to significantly increase the magnitude of calcium transients and spontaneous calcium sparks in isolated heart cells . This modulation of the CICR mechanism helps to recharge the sarcoplasmic reticulum’s calcium ion stores, ensuring efficient cardiac muscle contraction.

Mutations in the CASQ2 gene have been linked to various cardiac arrhythmias, including catecholaminergic polymorphic ventricular tachycardia (CPVT) . CPVT is a life-threatening condition characterized by irregular heart rhythms that can lead to sudden cardiac death. These mutations can disrupt the normal function of CASQ2, leading to mishandling of calcium ions within cardiac myocytes and contributing to the development of arrhythmic contractions .

Research into CASQ2 has provided valuable insights into its role in cardiac physiology and pathology. Studies have shown that CASQ2 can be regulated through phosphorylation and glycosylation modifications, which impact its ability to polymerize and buffer calcium ions . Understanding these regulatory mechanisms is crucial for developing potential therapeutic strategies for treating calcium-mediated arrhythmias and other cardiac disorders associated with CASQ2 dysfunction.