Figure 1.

Conceptual model of dynamic Ca²⁺-effector coupling in the endothelium and its real-time regulation of arterial tone. It is proposed that a discrete scaffold of IP₃Rs within the endoplasmic reticulum of the vascular intima establishes an intrinsic mode of dynamic Ca²⁺ signals. Relative shifts in IP₃ production define new profiles of dynamic signaling with respect to the number of sites as well as event amplitude, frequency, duration and spatial spread. The distribution and density of specific Ca²⁺-dependent effectors within the endothelium, including those that are tightly coupled to local Ca²⁺ origination sites (blue) such as K_Ca3.1 channels, and those that are more peripherally or widely distributed (yellow and green) such as K_Ca2.3 channels and eNOS, determine the ultimate level of vasodilating influence communicated across the internal elastic lamina (IEL) to the vascular smooth muscle (VSM) as well as the predominating mechanism solicited (i.e. NO vs. hyperpolarization). This suggests a basal dynamic Ca²⁺ signaling modality exerts a steadfast and predictable endothelial influence on arterial tone (dotted line) that is constantly tuned by prevailing conditions.