Model depicting the role of P2X₁ during platelet activation by low doses of collagen.

Platelets stimulated with low doses of collagen (1) rapidly release ATP, which activates a Ca⁺⁺- and PKC-dependent ERK2 pathway through P2X₁ (2) leading to further granule release and platelet aggregation (3). Both the PKC-dependent minor early secretion evoked by collagen and the PKC-dependent P2X₁-mediated ERK2 activation are inhibited by the PKC inhibitor GF109203-X; these GF109203-X–sensitive PKCs are indicated as PKC1 and PKC2 to refer to their sequential activation during platelet aggregation. The approaches that we used to interfere with the P2X₁-ERK2 pathway at different levels are indicated.