Linking the SUR1-TRPM4 channel to PAR1 signaling broadens the pathological implications of channel upregulation, since in ischemia, endogenous tPA/plasmin as well as thrombin both signal via PAR1, and may be responsible for receptor-induced MMP-9 secretion in the absence of exogenous (recombinant) tPA [68]. This evidence concerns the gene F2R and ischemia.