A wide range of studies have demonstrated that sub-sacrolemmal (SSL) Ca2+ homeostasis is tightly coupled to regionally localized Ca2+ stores providing unique mechanisms for regulating smooth muscle contractility. The relations between the plasma membrane and SSL Ca2+ stores have not been fully described, although key components such as Ca2+ sensitive K+ channels (1) and store operated Ca2+ channels (2) in the plasma membrane clearly are modulated by store activity in a localized fashion. The Na-Ca exchanger (NCX) is a key player in the regulation of store Ca2+ load, and as such its activity can modify the activity of Ca2+ sensitive channels in plasma membrane (3). Moreover, the activity of the Na-K ATPase (NKA) modulates intracellular Na+ which can alter the driving force for Ca2+ removal via NCX. Previous studies have demonstrated that the α2-isoform of NKA is localized in specific regions of the plasma membrane, and it is this isoform that specifically modulates NCX activity and loading of SSL Ca2+ stores (4). Earlier work also demonstrated that full activity of NKA is dependent on an active glycolytic pathway in vascular smooth muscle (5). The relations between Ca2+ store loading, the NCX / α2-NKA couple and glycolytic metabolism will be the focus of this presentation.