Controlling the Flow of Energy: Inhibition and Stimulation of the Creatine Transporter

Creatine in its free and phosphorylated form plays an essential role for maintenance and distribution of ATP levels in tissues with high and fluctuating energy demands such as muscle, brain and heart. Alterations in the creatine concentration in these tissues produce marked functional changes. Creatine concentration is largely determined by a specific creatine transporter, a member of the Na+ dependent transporters family, that is localized on the cells' plasma membrane. This transporter is needed to carry creatine into the cells against a high concentration gradient. In recent years the mechanisms regulating the expression and the function of this transporter are being unraveled. Even if our knowledge of this matter is still limited, we have now tools for either stimulating or inhibiting this transporter, tools that may be relevant to several experimental and clinical conditions. This review will examine the data and the tools that are available in relation to the regulation and expression of the creatine transporter. Furthermore, we will briefly review the possible practical relevance of manipulating the creatine transporter activity.