Partial inhibition of SERCA is responsible for extracellular [Ca.sup.2+] dependence of Al[F.sup.-.sub.4]-induced [[[Ca.sup.2+]].sub.i] oscillations in rat pancreatic acinar cells

Chong, Seon Ah, Soo Young Hong, Seok Jun Moon, Jee Won Park, Jeong-Hee Hong, Jeong Mi An, Syng-III Lee, Dong Min Shin, and Jeong Taeg Seo. Partial inhibition of SERCA is responsible for extracellular [Ca.sup.2.sup.+] dependence of [Al[F.sup.-.sub.4]-induced [[Ca.sup.2.sup.+].sub.i] oscillations in rat pancreatic acinar cells. Am J Physiol Cell Physiol 285: C1142-C1149, 2003. First published July 23, 2003; 10.1152/ajpcell.00566.2002. --[Al[F.sup.-.sub.4] is known to generate oscillations in intracellular [Ca.sup.2.sup.+] concentration [([Ca.sup.2.sup.+].sub.i)] by activating G proteins in many cell types. However, in rat pancreatic acinar cells, [Al[F.sup.-.sub.4]evoked [[Ca.sup.2.sup.+].sub.i] oscillations were reported to be dependent on extracellular [Ca.sup.2.sup.+], which contrasts with the [[Ca.sup.2.sup.+].sub.i] oscillations induced by cholecystokinin (CCK). Therefore, we investigated the mechanisms by which [Al[F.sup.-.sub.4] generates extracellular [Ca.sup.2.sup.+]-dependent [[Ca.sup.2.sup.+].sub.i] oscillations in rat pancreatic acinar cells. [Al[F.sup.-.sub.4]-induced [[Ca.sup.2.sup.+].sub.i] oscillations were stopped rapidly by the removal of extracellular [Ca.sup.2.sup.+] and were abolished on the addition of 20 mM caffeine and 2[micro]M thapsigargin, indicating that [Ca.sup.2.sup.+] influx plays a crucial role in maintenance of the oscillations and that an inositol 1,4,5-trisphos-phate-sensitive [Ca.sup.2.sup.+] store is also required. The amount of [Ca.sup.2.sup.+] in the intracellular [Ca.sup.2.sup.+] store was decreased as the [Al[F.sup.-.sub.4]-induced [[Ca.sup.2.sup.+].sub.i] oscillations continued. Measurement of [sup.45][Ca.sup.2.sup.+] influx into isolated microsomes revealed that [Al[F.sup.-.sub.4] directly inhibited sarco/endoplasmic reticulum [Ca.sup.2.sup.+]-ATPase (SERCA). The activity of plasma membrane [Ca.sup.2.sup.+]-ATPase during [Al[F.sup.-.sub.4] stimulation was not significantly different from that during CCK stimulation. After partial inhibition of SERCA with 1 nM thapsigargin, 20 pM CCK-evoked [[Ca.sup.2.sup.+].sub.i] oscillations were dependent on extracellular [Ca.sup.2.sup.+]. This study shows that [Al[F.sup.-.sub.4] induces [[Ca.sup.2.sup.+].sub.i] oscillations, probably by inositol 1,4,5-trisphosphate production via G protein activation but that these oscillations are strongly dependent on extracellular [Ca.sup.2.sup.+] as a result of the partial inhibition of SERCA. cholecystokinin; plasma membrane adenosine 5'-triphosphatase; G proteins; caffeine