CA2-TRISPHOSPHATE RECEPTORS( ENTRY INTO PC12 CELLS INITIATED BY RYANODINE RECEPTORS OR INOSITOL 1,4,5)

Capacitative Ca2+ entry (CCE) is a universal mechanism for refilling i ntracellular Ca2+ stores in electrically non-excitable cells. The situ ation in excitable cells is less clear, however, since they may rely o n other entry mechanisms for Ca2+-store refilling. In the present stud y we investigated CCE in intact PC12 cells, using acetylcholine to bri ng about activation of InsP(3) receptors (InsP,Rs), caffeine to activa te ryanodine receptors (RyRs) and thapsigargin to inhibit sarco/endopl asmic reticulum Ca2+-ATPase pumps. We found that depletion of the InsP (3)-, caffeine- or thapsigargin-sensitive stores promoted Ca2+ entry, suggesting that stimulation of either InsP(3)Rs or RyRs can activate C CE. The CCE pathways activated by InsP(3)Rs, RyRs and thapsigargin app eared to be independent at least in part, since their effects were fou nd to be additive. However, CCE triggered by caffeine, acetylcholine o r thapsigargin progressively diminished with time. The decay of CCE ca used by one agent also inhibited subsequent responses to the others, s uggesting that some component of the CCE pathway is common to all intr acellular Ca2+ stores. The magnitude of CCE stimulated by InsP(3)Rs or RyRs was related to the size of the stores; the InsP(3)-sensitive sto re was smaller than the RyR-sensitive store and triggered a smaller en try component. However, both stores filled with a similar half time (a bout 1 min), and both could be filled more rapidly by depolarization-i nduced Ca2+ entry through voltage-operated channels. A significant bas al Ca2+ influx was apparent in PC12 cells. The basal entry component m ay be under the control of the InsP(3)-sensitive Ca2+ store, since sho rt incubations in Ca2+-free medium depleted this store.