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 (ICRANC) which did not discriminate between monovalent cations. ICRANC 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 ICRANC. 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 ICRAC (Hoth, M., and Penner, R. (1992) Nature 355, 353-356) in its ion-selectivity, pharmacological profile, and single-channel conductance.
Krause
E
E
2. Physiologisches Institut, Universität des Saarlandes, D-66421, Homburg/Saar, Germany. schulz@med-ph.uni-sb.de
Pfeiffer
F
F
Schmid
A
A
Schulz
I
I
D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D004553:Electric Conductivity; D006873:Hydroquinones / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D007811:Lanthanum / Q000494:pharmacology; D008297:Male; D051379:Mice; D010179:Pancreas / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D006873:Hydroquinones; D007811:Lanthanum; D015544:Inositol 1,4,5-Trisphosphate; C018855:2-tert-butylhydroquinone; D000252:Calcium-Transporting ATPases; D000109:Acetylcholine; D002118:Calcium