Partial inhibition of SERCA is responsible for extracellular Ca2+ dependence of AlF-4-induced [Ca2+]i oscillations in rat pancreatic

Am J Physiol Cell Physiol. 2003 Nov;285(5):C1142-9. doi: 10.1152/ajpcell.00566.2002. Epub 2003 Jul 23.


AlF4-is known to generate oscillations in intracellular Ca2+ concentration ([Ca2+]i) by activating G proteins in many cell types. However, in rat pancreatic acinar cells, AlF4--evoked [Ca2+]i oscillations were reported to be dependent on extracellular Ca2+, which contrasts with the [Ca2+]i oscillations induced by cholecystokinin (CCK). Therefore, we investigated the mechanisms by which AlF4- generates extracellular Ca2+-dependent [Ca2+]i oscillations in rat pancreatic acinar cells. AlF4(-)-induced [Ca2+]i oscillations were stopped rapidly by the removal of extracellular Ca2+ and were abolished on the addition of 20 mM caffeine and 2 microM thapsigargin, indicating that Ca2+ influx plays a crucial role in maintenance of the oscillations and that an inositol 1,4,5-trisphosphate-sensitive Ca2+ store is also required. The amount of Ca2+ in the intracellular Ca2+ store was decreased as the AlF4--induced [Ca2+]i oscillations continued. Measurement of 45Ca2+ influx into isolated microsomes revealed that AlF4-directly inhibited sarco/endoplasmic reticulum Ca2+-ATPase (SERCA). The activity of plasma membrane Ca2+-ATPase during AlF4- stimulation was not significantly different from that during CCK stimulation. After partial inhibition of SERCA with 1 nM thapsigargin, 20 pM CCK-evoked [Ca2+]i oscillations were dependent on extracellular Ca2+. This study shows that AlF4- induces [Ca2+]i oscillations, probably by inositol 1,4,5-trisphosphate production via G protein activation but that these oscillations are strongly dependent on extracellular Ca2+ as a result of the partial inhibition of SERCA.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aluminum Compounds / pharmacology*
  • Animals
  • Calcium / physiology*
  • Calcium Signaling / drug effects*
  • Calcium Signaling / physiology
  • Calcium-Transporting ATPases / antagonists & inhibitors*
  • Calcium-Transporting ATPases / physiology*
  • Extracellular Fluid / drug effects
  • Extracellular Fluid / enzymology
  • Fluorides / pharmacology*
  • Male
  • Pancreas / cytology
  • Pancreas / drug effects*
  • Pancreas / enzymology*
  • Rats
  • Rats, Sprague-Dawley
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases


  • Aluminum Compounds
  • tetrafluoroaluminate
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Calcium-Transporting ATPases
  • Fluorides
  • Calcium