F2R and ischemia: Furthermore, multiple direct mechanisms activate these channels, including mechanical stimulation [89], caspases-dependent cleavage of the C-tail of Panx1 [81], hypotonicity, ischemia [73], or a secondary response to the activation of receptors ionotropic as P2X4, P2X7, and NMDAR, which are permeable to cations, including Na+, K+, and Ca2+ [83,88,90], or metabotropic receptors such as P2Y1, P2Y2, and P2Y6 [90], protease-activated receptor-1 (PAR-1), bradykinin B2 receptor (BDKRB2) [91], histamine H1 receptor (HRH1), and α1D-adrenergic receptors (α1D-AR) [92].