Depletion of intracellular calcium stores activates a calcium conducting nonselective cation current in mouse pancreatic acinar cells

Receptor-mediated Ca2+ release from inositol (1,4,5)trisphosphate (IP3) sensitive Ca2+ stores causes ''capacitative calcium entry'' in many cell types (Putney, J, W,, Jr, (1986) Cell Calcium 7, 1-12; Putney, J. W,, Jr, (1990) Cell Calcium 11, 611-624), We used patch clamp and fluorescence techniques in isolated mouse pancreatic acinar cells to identify ion currents and cytosolic calcium concentrations under conditions in which intracellular Ca2+ stores were emptied, We found that depletion of Ca2+ stores activated a calcium-release-activated nonselective cation current (I-CRANC) which did not discriminate between monovalent cations. I-CRANC possessed a significant conductance for Ca2+ and Ba2+, It was not inhibited by La3+, Gd3+, Co2+, or Cd2+ but was completely abolished by flufenamic acid or genistein, In whole cell and cell-attached recordings, a 40-45 pS nonselective cation channel was identified which was activated by Ca2+ store depletion, Calcium entry as detected by single cell fluorescence measurements with fluo-3 or fura-2, showed the same pharmacological properties as I-CRANC. We conclude that in mouse pancreatic acinar cells 40-45 pS nonselective cation channels serve as a pathway for capacitative Ca2+ entry. This entry pathway differs from the previously described I-CRAC (Hoth, M,, and Penner, R. (1992) Nature 355, 353-356) in its ion-selectivity, pharmacological profile, and single-channel conductance.