Endothelin-Dependent Actions in Cultured AT-1 Cardiac Myocytes

• DOI: 10.1161/01.res.78.4.724
• Publication Date: 2012-06-12T00:47:05Z
• Authors: Tianrong Jiang; Elena Pak; HongLu Zhang; Richard P. Kline; Susan F. Steinberg
• Keywords: Chelerythrine; Calcium in biology; BAPTA; Phorbol; Fura-2

Abstract The consequences of endothelin receptor activation were examined in atrial tumor myocytes derived from transgenic mice (AT-1 cells). Endothelin-1 (endothelin) stimulates phosphoinositide hydrolysis a dose-dependent manner. Endothelin also induces the rapid and transient translocation protein kinase C (PKC)-ε immunoreactivity soluble to particulate cell fraction. subcellular distributions PKCα PKCζ (also expressed by AT-1 cells) are not influenced endothelin. Using quantitative fluorescence microscopy with fura 2, we effects on intracellular calcium. In electrically driven myocytes, increase amplitude calcium transient. This is blocked both phorbol 12-myristate 13-acetate (PMA) pretreatment downregulate PKC inhibitor chelerythrine, arguing that PKCε plays critical role receptor–dependent increases mitogen-activated (MAPK). MAPK markedly attenuated PMA or pertussis toxin (PTX, inactivate susceptible G α subunits); it completely prevented combined PTX. contrast, chelation BAPTA. These findings indicate pathway for stimulation involves PTX-sensitive protein(s). Thus, these studies identify functional as mediator cytosolic activity cells. Accordingly, system should provide uniquely useful model targets investigate their function regulation homeostasis induction growth response cardiac myocytes.