Expression and subcellular localization of the ryanodine receptor in rat pancreatic acinar cells

Abstract

The ryanodine receptor (RyR) is the principal Ca2+-release channel in excitable cells, whereas the inositol 1,4,5-trisphosphate (InsP3) receptor (InsP3R) is primarily responsible for Ca2+ release in non-excitable cells, including epithelia. RyR also is expressed in a number of non-excitable cell types, but is thought to serve as an auxiliary or alternative Ca2+-release pathway in those cells. Here we use reverse transcription PCR to show that a polarized epithelium, the pancreatic acinar cell, expresses the type 2, but not the type 1 or 3, isoform of RyR. We furthermore use immunochemistry to demonstrate that the type 2 RyR is distributed throughout the basolateral and, to a lesser extent, the apical region of the acinar cell, but is excluded from the trigger zone, where cytosolic Ca2+ signals originate in this cell type. Since propagation of Ca2+ waves in acinar cells is sensitive to ryanodine, caffeine and Ca2+, these findings suggest that Ca2+ waves in this cell type result from the co-ordinated release of Ca2+, first from InsP3Rs in the trigger zone, then from RyRs elsewhere in the cell. RyR may play a fundamental role in Ca2+ signalling in polarized epithelia, including for Ca2+ signals initiated by InsP3.

Generation and modulation of cytosolic Ca2+ signals in pancreatic acinar cells: techniques and mechanisms

“…Ashby et al [21] showed that both IP 3 and ryanodine-sensitive channels are present in the apical pole of the acinar cell. This finding is in agreement both with other functional studies that place these receptors in the apical pole [7,8] and with the results of immunostaining of the acinar cells [9,10,26]. Uncaging of Ca 2+ in the apical pole triggered an increase in cytosolic Ca 2+ that originates in the apical pole, and spreads to the basal pole.…”

Ca2+release dynamics in parotid and pancreatic exocrine acinar cells evoked by spatially limited flash photolysis

“…Following more intense stimulation, the Ca 2ϩ signals can propagate in a manner typical of a true "wave" toward the basal aspects of the cell; i.e., constant wave speed typical of an "all or nothing" phenomenon dependent on Ca 2ϩ -induced Ca 2ϩ release (CICR) (17,24,25,27,35,45). CICR can occur through either InsP 3 R or through the classical CICR channel, the ryanodine receptor (RyR), which is also expressed in exocrine cells (14,26,39,53). In pancreatic acinar cells, two general models have been proposed to account for the propagation of the Ca 2ϩ wave.…”

Modelling mechanism of calcium oscillations in pancreatic acinar cells

“…The rat pancreatic acinar cells express multiple isoforms of RyR Ashby and Tepikin 2002;Ashby et al 2003) but predominance with type II RyR (Leite et al 1999). The dynamic model of RyR has not been yet developed for pancreatic acinar cell.…”

“…In the pancreatic acinar cell the RyR receptors are distributed throughout the cell (Leite et al 1999;Ashby and Tepikin 2002;Ashby et al 2003). Thus it is important to incorporate RyR receptors in our model.…”