The effect of hypoxia on the phosphorylation of contractile and other proteins in perfused rat heart challenged by isoprenaline
England, P.J.; Krause, E.G.
Biomedica Biochimica Acta 46(5): 369-380
1987
ISSN/ISBN: 0232-766X PMID: 2822035 Document Number: 292213
Rat hearts perfused with 32Pi were made hypoxic by perfusion with medium gassed with N2/CO2 (19:1). There was a rapid decrease in tension development (25% of control within 40 s), but little change in the frequency of contraction, time to peak tension, or rate of relaxation. The phosphorylation of troponin-I, C-protein and myosin P-light chain was unaffected by 5 min of hypoxia, whereas the proportions of glycogen phosphorylase and pyruvate dehydrogenase in the active form increased slowly. When aerobically perfused hearts were challenged with a bolus (70 pmole) of D,L-isoprenaline, there was a large increase in contractile force, cyclic AMP concentration, phosphorylation of troponin-I and C-protein and activation of phosphorylase and pyruvate dehydrogenase. Hypoxia for 5 min caused a slight, progressive decrease in the response to isoprenaline of force, cyclic AMP and activation of phosphorylase and pyruvate dehydrogenase. In contrast, there was a larger decrease in the phosphorylation of troponin-I and C-protein, suggesting that the activity of cyclic AMP-dependent protein kinase towards the contractile proteins may be impaired by hypoxia. The phosphorylation of myosin P-light chain was unaltered by any condition. The response to hypoxia is compared to that of ischaemia, where a complete loss of the response to isoprenaline occurs after 5 min.