Fig. 10.

Schematic demonstrating proposed mechanism of ET-1-induced Ca²⁺ influx in chronically hypoxic pulmonary arterial smooth muscle cells. ET-1 binds to either ET_A or ET_B receptors, leading to activation of protein kinase C (PKC), with resulting activation of tyrosine kinases (TK) and Rho kinase. Activation of Rho kinase then causes activation of voltage-dependent Ca²⁺ channels (VDCC) and an increase in intracellular calcium concentration ([Ca²⁺]_i). PMA, phorbol 12-myristate 13-acetate; GTP-γ-S, guanosine 5′-[γ-thio]triphosphate; TA23, tyrphosin A23; KRB, Krebs solution.