Low level of sarcolemmal phosphatidylinositol 4,5-bisphosphate in cardiomyopathic hamster (UM-X7.1) heart

Objective: Phosphatidylinositol 4,5-bisphosphate (PtdIns 4,5-P-2) is not on ly a precursor to inositol 1,4,5-trisphosphate (Ins 1,4,5-P-3) and sn-1,2 d iacylglycerol, but also essential for the function of several membrane prot eins. The aim of this study was to evaluate the changes in the level of thi s phospholipid in the cell plasma membrane (sarcolemma, SL) of cardiomyopat hic hamster (CMPH) heart. Methods: We examined the cardiac SL PtdIns 4,5-P- 2 mass and the activities of the enzymes responsible for its synthesis and hydrolysis in 250-day-old UM-X7.1 CMPH at a severe stage of congestive hear t failure (CHF) and in age-matched controls (Syrian Golden hamsters). Resul ts: The SL PtdIns 4,5-P-2 mass in CMPH was reduced by 72% of the control va lue. The activities of PtdIns 4 kinase and PtdIns 4-P 5 kinase were depress ed by 69 and 50% of control values, respectively. Although, the total phosp holipase C (PLC) activity was moderately, although significantly, decreased (by 18% of control), PLC delta (1) isoenzyme activity in the SL membrane w as elevated, with a concomitant increase in its protein content, whereas PL C beta (1) and gamma (1) isoenzyme activities were depressed despite the in crease in their protein revels. A 2-fold increase in the Ins 1,4,5-P-3 conc entration in the cytosol of the failing heart of CMPH was also observed. Co nclusions: Reduced SL level of PtdIns 4,5-P-2 may severely jeopardize cardi ac cell function in this hamster model of CHF. In addition, the profound ch anges in the profile of heart SL PLC isoenzyme could alter the complex seco nd messenger responses of these isoenzymes, and elevated Ins 1,4,5-P-3 leve ls may contribute to intracellular Ca2+ overload in the failing cardiomyocy te. (C) 2001 Elsevier Science BN; All rights reserved.