CA2+ RELEASE INDUCED BY INOSITOL 1,4,5-TRISPHOSPHATE IS A STEADY-STATE PHENOMENON CONTROLLED BY LUMINAL CA2+ IN PERMEABILIZED CELLS

Article

关键词: SMOOTH-MUSCLE CELLS;    CALCIUM RELEASE;    CA-2+ RELEASE;    RAT;    STORES;    TRISPHOSPHATE;    PHOSPHATES;    KINETICS;    ENTRY;   

DOI  :  10.1038/357599a0

来源: SCIE

【 摘 要 】

Low concentrations of inositol 1,4,5-trisphosphate (InsP3) evoke a very rapid mobilization of intracellular Ca2+ stores in many cell types, which can be followed by a further, much slower efflux 1-8. Two explanations have been suggested for this biphasic release. The first proposes that the Ca2+ stores vary in their sensitivity to InsP3, and each store releases either its entire contents or nothing 2,5,7 (all-or-none release); the second proposes instead that the stores are uniformly sensitive to the effects of InsP3, but that they can release only a fraction of their Ca2+ before their sensitivity is somehow attenuated 6,8-11 (steady-state release). Experiments using purified InsP3 receptor molecules reconstituted into lipid vesicles have shown heterogeneity of the receptors in their response to InsP3 under conditions in which the total Ca2+ level at both sides of the receptor is held constant 7. We now report that in permeabilized A7r5 smooth-muscle cells incubated in Ca2+-free medium, the amount of Ca-45(2+) remaining in the stores after the rapid transient phase of release is independent of their initial Ca2+ levels, indicating that partially depleted stores are less sensitive to InsP3. Moreover, if the stores are reloaded with Ca-40(2+) after the first stimulus, reapplication of the same low concentration of InsP3 will release further Ca-45(2+). This recovery of InsP3 sensitivity is almost complete. Under these conditions, Ca2+ release must thus occur by a steady-state mechanism, in which the decreasing Ca2+ content of the stores slows down further release.

【 授权许可】

Free