Figure 3

Scheme of the serotonin signal pathway showing the steps in fenestral contraction and relaxation, as postulated by Gatmaitan et al.[89, 90, 104]: Serotonin binds to a ketanserin-inhibitable receptor, coupled to a pertussis-toxin sensitive G-protein; a calcium channel opens, causing an influx of calcium ions; the intracellular calcium level increases rapidly, and calcium binds to calmodulin; the calcium-calmodulin complex activates myosin light chain kinase, and as a result phosphorylation of the 20-kd light chain of myosin occurs, resulting in an increased actin-activated myosin ATPase activity, which finally initiates contraction of fenestrae. The mechanism for the relaxation of LSEC fenestrae is presently unclear and probably involves dephosphorylation of myosin light chains as represented by dashed lines: a decrease in the cytosolic free calcium concentration leads to dissociation of calcium and calmodulin from the kinase, thereby inactivating myosin light chain kinase, under these conditions myosin light chain phosphatase, which is not dependent on calcium for activity, dephosphorylates myosin light chain and finally causes relaxation of fenestrae.