Acute exposure of ceramide enhances cardiac contractile function in isolated ventricular myocytes

The sphingolipid ceramide, a primary building block for all other sphingolipids, is associated with growth arrest, apoptosis, and lipotoxic dysfunction. Interestingly, ceramide may attenuate high glucose‐induced myocyte dysfunction, produce Ca 2+ influx, and augment smooth muscle contraction. To determine the role of ceramide on cardiac excitation–contraction (E–C) coupling, electrically paced adult rat ventricular myocytes were acutely exposed to a cell‐permeable ceramide analog (10 p M –100 μ M ) and the following indices were determined: peak shortening (PS), time‐to‐P., time‐to‐90% relengthening, and the maximal velocity of shortening and relengthening (± d L d t). Intracellular Ca 2+ properties were assessed using fura‐2AM fluorescent microscopy. Our results revealed a concentration‐ and time‐dependent increase of PS in ventricular myocytes in response to ceramide associated with an increase in ± d L d t. The maximal increase in PS was ∼35% from control value and was maintained throughout the first 20 min of ceramide exposure. However, the ceramide‐induced increase in PS was not maintained once the exposure time was beyond 20 min. Acute exposure of ceramide significantly enhanced intracellular Ca 2+ release, although at a much lower concentration range. The ceramide‐induced augmentation of PS was not significantly affected by inhibition of phosphatidylinositol (PI)‐3‐kinase, protein kinase C (PKC), ceramide‐activated protein phosphatase (CAPP), and nitric oxide (NO) synthase. Our data suggest that ceramide acutely augments the contractile function of cardiac myocytes through an alternative mechanism(s) rather than PI‐3‐kinase, PKC, CAPP, or NO.British Journal of Pharmacology (2003) 140 , 1163–1168. doi: 10.1038/sj.bjp.0705510