Interaction with the inositol 1,4,5‐trisphosphate receptor promotes Ca2+ sequestration in permeabilised insulin‐secreting cells

FEBS Letters

Rorsman, Patrik¹  Berggren, Per-Olof¹  Nilsson, Thomas¹  Islam, Md.Shahidul¹ 

[1] The Rolf Luft Center for Diabetes Research, Department of Endocrinology, Karolinska Institute, Box 60500, Karolinska Hospital, S-104 01 Stockholm, Sweden

关键词: Inositol 1;    4;    5-trisphospate;    Inositol 1;    4;    5-trisphosphate receptor;    Intracellular Ca2+-transport;    Insulin-secreting cell;   

DOI  :  10.1016/0014-5793(91)80995-F

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Electropermeabilised insulin-secreting RINm5F cells sequestered Ca²⁺, resulting in a steady-state level of the ambient free Ca²⁺ concentration corresponding to 723 ± 127 nM (mean ± SEM, n = 10), as monitored by a Ca²⁺-selective minielectrode. Inositol 1,4,5-trisphosphate (Ins(1,4,5)P₃) promoted a rapid and pronounced release of Ca²⁺. This Ca²⁺ was resequestered and a new steady-state Ca²⁺ level was attained, which was always lower (460 ± 102 nM, n = 10, P < 0.001) than the steady-state Ca²⁺ level maintained before the addition of Ins(1,4,5)P₃. Whereas the initial reuptake of Ca²⁺ subsequent to Ins(1,4,5,)P₃ stimulation was relatively slow, the later part of reuptake was fast as compared to the reuptake phases of a pulse addition of extraneous Ca²⁺. In the latter case the uptake of Ca²⁺ resulted in a steady-state level similar to that found in the absence of Ins(1,4,5)P₃. Addition of Ins(1,4,5)P₃ under this condition resulted in a further Ca²⁺ uptake and thus a lower steady-state Ca²⁺ level, Heparin, which binds to the Ins(1,4,5)P₃ receptor, also lowered the steady-state free Ca²⁺ concentration, In contrast to Ins(1,4,5)P₃ inositol 1,3,4,5-tetrakis-phosphate was without effect on Ca²⁺ sequestration. These findings are consistent with the presence of a high-affinity Ins(1,4,5)P₃ receptor promoting continuous release of Ca²⁺ under basal conditions and/or the Ins(1,4,5)P₃ receptor being actively involved in Ca²⁺ sequestration.

【 授权许可】

Unknown