Changes in intracellular calcium induced by acute hypothermia in parenchymal, endothelial, and Kupffer cells of the rat liver

Disturbances in intracellular calcium have been implicated in liver graft d amage after cold preservation and warm reperfusion. Despite improvements no ted with the use of calcium channel blockers, such as nisoldipine, the exac t nature and cellular basis of the presumed changes in intracellular calciu m as well as the actual target of these blockers remain unclear. Isolated r at parenchymal, endothelial, and Kupffer cells were cultured and changes in intracellular calcium measured in vitro after acute hypothermia (5-8 degre es C) by fluorescence imaging using FURA-2. Between 50 and 80% of parenchym al, endothelial, and Kupffer cells exhibited significant increases in basel ine calcium that were gradual and sustained for the duration of acute hypot hermia. Removal of extracellular calcium completely abolished the positive response of hepatocytes and diminished the proportion of responding endothe lial and Kupffer cells. The calcium channel blocker nisoldipine (1 mu M) sl ightly diminished the proportion of positive responders in parenchymal but not in endothelial or Kupffer cells. However, nisoldipine did not modify th e amplitude of the calcium rise in responding cells of all types. Acute hyp othermia causes calcium influx into a majority of parenchymal, endothelial, and Kupffer cells. Nisoldipine does not effectively prevent these changes in intracellular calcium. Pathways of calcium entry resistant to the drug o r other than voltage-dependent calcium channels may thus be involved. (C) 1 999 Academic Press.