Berridge M J
Babraham Institute Laboratory of Molecular Signalling, Department of Zoology, Cambridge University, U.K.
Biochem J. 1994 Sep 1;302 ( Pt 2)(Pt 2):545-50. doi: 10.1042/bj3020545.
Following stimulation with a calcium-mobilizing agonist there is often a distinct latency (L) preceding the onset of the first calcium spike. In the continued presence of the agonist, repetitive spikes appear separated by a variable period (P). The relationship between L and P has been investigated in an insect salivary gland responding to 5-hydroxytryptamine (5-HT). Both L and P were found to decrease as the concentration of 5-HT was increased over its physiological range of 1-10 nM. Lowering the concentration of external calcium from 1 x 10(-3) M to 1 x 10(-5) M increased both P and L. However, the effect on L was apparent only at low levels of 5-HT. Reducing the content of the internal stores by repeated stimulation in a calcium-free medium resulted in a progressive prolongation of L. On the other hand, the effect of L decreased when glands were stimulated repetitively in normal calcium-containing medium. All these results are consistent with a hypothesis that calcium plays a critical role in determining the kinetics of calcium release during both L and P. An important component seems to be the entry of external calcium, which sets the stage for calcium release by loading up the internal stores. As these stores fill up with calcium, the Ins(1,4,5)P3 receptors will initiate a calcium spike once they become sensitized to the ambient level of Ins(1,4,5)P3.
在用钙动员激动剂刺激后,在第一个钙峰出现之前通常有一个明显的延迟期(L)。在激动剂持续存在的情况下,重复的钙峰出现,其间隔时间可变(P)。在对5-羟色胺(5-HT)产生反应的昆虫唾液腺中,研究了L和P之间的关系。发现在5-HT的生理浓度范围1-10 nM内,随着5-HT浓度的增加,L和P均降低。将细胞外钙浓度从1×10⁻³ M降至1×10⁻⁵ M会使P和L均增加。然而,对L的影响仅在低水平的5-HT时才明显。通过在无钙培养基中反复刺激来降低内部钙库的含量,会导致L逐渐延长。另一方面,当在正常含钙培养基中对腺体进行反复刺激时,L的影响会降低。所有这些结果都与一个假设一致,即钙在决定L期和P期钙释放的动力学过程中起关键作用。一个重要的因素似乎是细胞外钙的内流,它通过填充内部钙库为钙释放奠定了基础。随着这些钙库充满钙,一旦1,4,5-三磷酸肌醇(Ins(1,4,5)P3)受体对环境中的Ins(1,4,5)P3水平变得敏感,它们就会引发一个钙峰。