Mechanism of receptor-oriented intercellular calcium wave propagation in hepatocytes

被引:74
作者
Dupont, G
Tordjmann, T
Clair, C
Swillens, S
Claret, M
Combettes, L
机构
[1] Univ Paris 11, Unite Rech U442, Inst Natl Rech Sci Sante, F-91405 Orsay, France
[2] Free Univ Brussels, Fac Sci CP231, B-1050 Brussels, Belgium
[3] Free Univ Brussels, IRIBHN, Fac Med, B-1050 Brussels, Belgium
关键词
liver; phase wave; gap junctions; inositol 1,4,5-triphosphate;
D O I
10.1096/fasebj.14.2.279
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Intercellular calcium signals are propagated in multicellular hepatocyte systems as well as in the intact liver, The stimulation of connected hepatocytes by glycogenolytic agonists induces reproducible sequences of intracellular calcium concentration increases, resulting in unidirectional intercellular calcium waves. Hepatocytes are characterized by a gradient of vasopressin binding sites from the periportal to perivenous areas of the cell plate in hepatic lobules, Also, coordination of calcium signals between neighboring cells requires the presence of the agonist at each cell surface as well as gap junction permeability, We present a model based on the junctional coupling of several hepatocytes differing in sensitivity to the agonist and thus in the intrinsic period of calcium oscillations. In this model, each hepatocyte displays repetitive calcium spikes with a slight phase shift with respect to neighboring cells, giving rise to a phase wave. The orientation of the apparent calcium wave is imposed by the direction of the gradient of hormonal sensitivity. Calcium spikes are coordinated by the diffusion across junctions of small amounts of inositol 1,4,5-trisphosphate (InsP(3)), Theoretical predictions from this model are confirmed experimentally. Thus, major physiological insights may be gained from this model for coordination and spatial orientation of intercellular signals.
引用
收藏
页码:279 / 289
页数:11
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