PKC activation increases Ca^sup 2+^ sensitivity of permeabilized lymphatic muscle via myosin light chain 20 phosphorylation-dependent and -independent mechanisms

The contractile activity of muscle cells lining the walls of collecting lymphatics is responsible for generating and regulating flow within the lymphatic system. Activation of PKC signaling contributes to the regulation of smooth muscle contraction by enhancing sensitivity of the contractile apparatus to ... It is currently unknown whether PKC signaling contributes to the regulation of lymphatic muscle contraction. We hypothesized that the activation of PKC signaling would increase the sensitivity of the lymphatic myofilament to ... To test this hypothesis, we determined the effects of PKC activation with phorbol esters [PMA or phorbol dibutyrate (PDBu)] on the contractile behavior of α-toxin-permeabilized rat mesenteric and cervical lymphatics or the thoracic duct. The addition of PMA or PDBu induced a significant increase in the contractile force of submaximally activated α-toxin-permeabilized lymphatic muscle independent of a change in intracellular ... concentration, and the ...-force relationship of lymphatic muscle was significantly left shifted, indicating greater myofilament ... sensitivity. Phorbol esters increased the maximal rate of force development, whereas the rate of relaxation was reduced. Western blot and immunohistochemistry data indicated that the initial rapid increase in tension development after stimulation by PDBu was associated with myosin light chain ... phosphorylation; however, the later, steady-state ... sensitization of permeabilized lymphatic muscle was not associated with increased phosphorylation of ... at ..., 17-kDa C-kinase-potentiated protein phosphatase-1 inhibitor at ..., or caldesmon at ... Thus, these data indicate that PKC-dependent ... sensitization of lymphatic muscle may involve ... phosphorylation-dependent and -independent mechanism(s). (ProQuest: ... denotes formulae/symbols omitted.)