The effect of inositol 1,3,4,5-tetrakisphosphate on inositol trisphosphate-induced Ca2+ mobilization in freshly isolated and cultured mouse lacrimal acinar cells

Earlier reports have shown a remarkable synergism between InsP₄ and InsP₃ [either Ins(1,4,5)P₃ or Ins(2,4,5)P₃] in activating Ca²⁺-dependent K⁺ and Cl^- currents in mouse lacrimal cells [Changya, Gallacher, Irvine, Potter and Petersen (1989) J. Membr. Biol. 109, 85-93; Smith (1992) Biochem. J. 283, 27-30]. However, Bird, Rossier, Hughes, Shears, Armstrong and Putney [(1991) Nature (London) 352, 162-165] reported that they could see no such synergism in the same cell type. A major experimental difference between the two laboratories lies in whether or not the cells were maintained in primary culture before use. Here we have compared directly the responses to inositol polyphosphates in freshly isolated cells versus cells cultured for 6-72 h. In the cultured cells, Ins(2,4,5)P₃ at 100 μM produced a robust stimulation of K⁺ and Cl^- currents, as much as an order of magnitude greater than that observed in the freshly isolated cells. However, the freshly isolated cells could be restored to a sensitivity similar to cultured cells by the addition of InsP₄ at a concentration two orders of magnitude lower than that of Ins(2,4,5)P₃. We discuss the implications of this with respect to the actions of InsP₄, including the possibility that disruption of the cellular structure during the isolation of the cells exposes an extreme manifestation of a possible physiological role for InsP₄ in controlling calcium-store integrity.