A REEVALUATION OF THE APPARENT EFFECTS OF LUMINAL CA2-TRISPHOSPHATE-INDUCED CA2+ RELEASE( ON INOSITOL 1,4,5)

It has been suggested that the release of Ca2+ from intracellular stor es by 2+ inositol 1,4,5-trisphosphate (InsP(3)) is modulated by the lu minal Ca2+ content of the stores and that such an effect could underli e the apparent 'quantal' nature of InsP(3)-induced release. Although i nitial studies failed to find evidence in support of such a modulation , several subsequent reports have indicated luminal Ca2+ effects that become apparent only after a greater than 70-75% depletion of Ca2+ sto res, In these studies, Ca2+ release was expressed as a percentage of a n A23187-releasable pool which comprised both InsP(3)-sensitive and In sP(3)-insensitive components, In model calculations we have found that the presence of even a minor InsP(3)-insensitive component in the tot al Ca2+ pool significantly distorts interpretation of the data, We sho w that the published results can be accurately duplicated without any requirement for a shift in the true InsP(3) sensitivity of Ca2+ releas e if either: (a) the InsP(3)-insensitive component does not remain a c onstant proportion of the total pool during depletion (i.e. depletion disproportionally affects the InsP(3)-sensitive component); or (b) dur ing generation of InsP(3)-response curves, additional Ca2+ is released from the InsP(3)-insensitive component as the InsP(3)-sensitive compo nent is progressively emptied, Examination indicates that either, or b oth, of these conditions apply in the published reports and we conclud e that the demonstrated effects of luminal Ca2+ may be artifacts.