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APJ downstream signaling pathways for Ca2+ independent positive inotropic effect (PIE) and length-dependent activation (LDA). Apelin-induced activation of APJ enhances myofilament sensitivity to Ca2+, which leads to the positive regulation of LDA. The mechanisms include intracellular alkalinization by Gαq-dependent NHE-1 activation (red arrows), Gαi-dependent dephosphorylation of cTnI (black dashed arrows), and the phosphorylation of MLC (blue arrows, mechanism unknown).
