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 damage after cold preservation and warm reperfusion. Despite improvements noted with the use of calcium channel blockers, such as nisoldipine, the exact nature and cellular basis of the presumed changes in intracellular calcium as well as the actual target of these blockers remain unclear. Isolated rat parenchymal, endothelial, and Kupffer cells were cultured and changes in intracellular calcium measured in vitro after acute hypothermia (5-8 degrees C) by fluorescence imaging using FURA-2. Between 50 and 80% of parenchymal, endothelial, and Kupffer cells exhibited significant increases in baseline calcium that were gradual and sustained for the duration of acute hypothermia. Removal of extracellular calcium completely abolished the positive response of hepatocytes and diminished the proportion of responding endothelial and Kupffer cells. The calcium channel blocker nisoldipine (1 microM) slightly diminished the proportion of positive responders in parenchymal but not in endothelial or Kupffer cells. However, nisoldipine did not modify the amplitude of the calcium rise in responding cells of all types. Acute hypothermia 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 or other than voltage-dependent calcium channels may thus be involved.
Haddad
P
P
Centre Hospitalier de l'Université de Montréal, Campus Saint-Luc, Université de Montréal, Montréal, Québec, H3C 3J7, Canada.
Cabrillac
J C
JC
Piche
D
D
Musallam
L
L
Huet
P M
PM
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015925:Cryopreservation; D004727:Endothelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007036:Hypothermia, Induced; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D016031:Liver Transplantation; D008297:Male; D015737:Nisoldipine / Q000494:pharmacology; D009926:Organ Preservation; D051381:Rats
D002121:Calcium Channel Blockers; D015737:Nisoldipine; D002118:Calcium