Thapsigargin causes Ca2+ release and collapse of the membrane potential of Trypanosoma brucei mitochondria in situ and of isolated rat liver mitochondria.
Thapsigargin, previously reported to release Ca2+ from non-mitochondrial stores of different cell types, as well as nigericin, were found, when used at high concentrations, to release Ca2+ and collapse the membrane potential of Trypanosoma brucei bloodstream and procyclic trypomastigotes mitochondria in situ. At similarly high concentrations (> 10 microM), thapsigargin was also found to release Ca2+ and collapse the membrane potential of isolated rat liver mitochondria. These results indicate that care should be taken when attributing the effects of thapsigargin in intact cells to the specific inhibition of the sarcoplasmic and endoplasmic reticulum Ca(2+)-ATPase family of calcium pumps. In addition, we have found no evidence for an increase in intracellular Ca2+ by release of the ion from intracellular stores by nigericin, measuring changes in cytosolic Ca2+ by dual wavelength spectrofluorometry in fura-2-loaded T. brucei bloodstream trypomastigotes or measuring Ca2+ transport in digitonin-permeabilized cells.
Vercesi
A E
AE
Department of Veterinary Pathobiology, University of Illinois, Urbana 61801.
Moreno
S N
SN
Bernardes
C F
CF
Meinicke
A R
AR
Fernandes
E C
EC
Docampo
R
R
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004072:Digitonin / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D009550:Nigericin / Q000494:pharmacology; D051381:Rats; D013729:Terpenes / Q000494:pharmacology*; D019284:Thapsigargin; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism
D013729:Terpenes; D019284:Thapsigargin; D004072:Digitonin; D009550:Nigericin; D002118:Calcium