Ca2+ dynamics of thrombin-stimulated rat heart-derived embryonic myocytes: relationship to protein synthesis and cell growth.
Various cell types respond to the serum protease, thrombin, with increased proliferation rates. In non-dividing postnatal mammalian cardiomyocytes, however, thrombin induces cellular hypertrophy. Both growth responses are associated with early Ca2+ signaling. The present study was conducted to characterize Ca2+ dynamics in thrombin stimulated, dividing embryonic cardiomyocytes, and to ascertain whether such dynamics support hypertrophic or hyperplastic growth. H9c2 rat cardiomyoblasts responded to thrombin with immediate, large increments in free Ca2+ that arose principally from the release of S(E)R sequestered Ca2+ and that persisted for only a few min. Ca2+ stores were refilled within 1h. Thrombin also increased rates of overall protein synthesis for several hours. This translational up-regulation, which required gene transcription, was abolished if cells were incubated at low extracellular Ca2+ during the first hour with thrombin. The protease conferred protective effects against toxicity resulting from serum deprivation and doxorubicin treatment. However, thrombin induced neither cellular hypertrophy, as is seen with arginine vasopressin, nor hyperplasia, as is observed with platelet-derived growth factor (PDGF-BB), in H9c2 cardiomyocytes. In comparison with vasopressin or PDGF-BB, thrombin promoted brief Ca2+ signaling, little cation movement to the extracellular fluid, and more rapid refilling of the S(E)R. It is concluded that the Ca2+ signaling generated by thrombin and the translational stimulation shown in this report to depend on this Ca2+ signaling are insufficient to sustain a major growth response in these embryonic cardiomyocytes.
Brostrom
Margaret A
MA
Department of Pharmacologya, U.M.D.N.J.-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA. brostrom@umdnj.edu
Pan
Zui
Z
Meiners
Sally
S
Drumm
Christopher
C
Ahmed
Ijaz
I
Brostrom
Charles O
CO
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D045604:Extracellular Fluid / Q000737:chemistry; D006321:Heart / Q000187:drug effects / Q000196:embryology*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D051381:Rats; D013917:Thrombin / Q000494:pharmacology*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
D013917:Thrombin; D002118:Calcium