Potential Role of αKAP, a CaMKII Kinase Anchoring Protein in Myocardium

• Main Author: Hawari, Omar
• Language: en
• Published: 2013
• Subjects: CaMKII; cardiomyocytes; SERCA2a; αKAP; Anchoring protein; cardiac contraction
• Online Access: http://hdl.handle.net/10393/24299

The Sarco-endoplasmic Ca2+ ATPase (SERCA2a) plays a crucial role in sequestering cytosolic calcium into the sarco-endoplasmic reticulum (SR/ER) and is an important regulator of muscle contraction and relaxation. Recent findings suggest that a novel CAMKIIα splice variant, αKAP, that plays the role of a CAMKII anchoring protein in the myocardium, also directly interacts with SERCA2a. We examined the effects of αKAP on SERCA2a activity using transfection of HEK-293T cells as well as lentiviral infection of primary neonatal mouse cardiomyocytes (NMCM). Our data showed that αKAP reduced Ca2+ ATPase activity, and downregulated SERCA2a expression in both HEK-293T cells coexpressing αKAP and SERCA2a, as well as NMCM overexpressing αKAP. Interestingly in a rat model of myocardial infarction, αKAP expression was found to be elevated, alongside elevated CaMKIIδ, and depressed SERCA2a expression. These data suggest that αKAP may be a unique regulator of SERCA2a activity and cardiac function.