Abstract
Calcium （Ca2+） is an important intracellular messenger that regulates myocyte contraction via excitation-contraction （E-C） coupling and gene transcription underlying cardiac hypertrophy. The mechanisms of E-C coupling in immature hearts are believed to be different from those in adult hearts because of the structural immaturity of the sarcoplasmic reticulum （SR） and T-tubules in an immature heart; however, the details of these mechanisms are not completely understood. Neuronal Ca2+ sensor-1 （NCS-1） is an EF-hand Ca2+-binding protein, which is an important regulator of neuronal functions. Although NCS-1 is expressed in high levels in immature hearts, only little is known about its cardiac functions. In this study, two novel functions of NCS-1 in cardiac tissue was discovered by characterizing the cardiac phenotypes of knockout （Ncs1－/－） mice. NCS-1 was found to be a regulator of contraction in immature hearts and that of hypertrophy in adult hearts. NCS-1 promotes Ca2+ release from the inositol trisphosphate receptors （IP3Rs）, followed by Ca2+/calmodulin-dependent protein kinase II signaling, which results in a large increase in the SR Ca2+ content in an immature heart. In addition, NCS-1 expression increased during the early stages of hypertrophy in the adult heart; and phenylephrine-induced cardiac hypertrophy was largely attenuated in Ncs1－/－ hearts. Our results revealed a novel mechanism of E-C coupling in immature hearts and another regulatory mechanism involved in the progression of receptor stimulation-elicited cardiac hypertrophy.
