Figure 10. Proposed concept for a conducted response propagated via endothelial Cx40 in HPV.

The scheme encompasses (i) proposed signaling events at the level of the alveolar site of gas exchange (left), in which hypoxia induces endothelial membrane depolarization (E_m↑) in lung capillaries, potentially by inhibition of oxygen-sensitive K_v channels; (ii) retrograde propagation of endothelial membrane depolarization from alveolar capillaries to upstream arterioles via Cx40 (middle), and (iii) elicitation of a vasoconstrictive response at the level of the upstream arteriole (right) through activation of the α_1G subtype T type VDCC, subsequent activation of cPLA₂, and formation of EETs, which may serve as either direct (intercellular) or indirect (intracellular) mediators of smooth muscle cell contraction.