Molecular mechanisms of intracellular calcium excitability in X. laevis oocytes.
Following receptor activation in Xenopus oocytes, spiral waves of intracellular Ca2+ release were observed. We have identified key molecular elements in the pathway that give rise to Ca2+ excitability. The patterns of Ca2+ release produced by GTP-gamma-S and by inositol 1,4,5-trisphosphate (IP3) are indistinguishable from receptor-induced Ca2+ patterns. The regenerative Ca2+ activity is critically dependent on the presence of IP3 and on the concentration of intracellular Ca2+, but is independent of extracellular Ca2+. Broad regions of the intracellular milieu can be synchronously excited to initiate Ca2+ waves and produce pulsating foci of Ca2+ release. By testing the temperature dependence of wavefront propagation, we provide evidence for an underlying process limited by diffusion, consistent with the elementary theory of excitable media. We propose a model for intracellular Ca2+ signaling in which wave propagation is controlled by IP3-mediated Ca2+ release from internal stores, but is modulated by the cytoplasmic concentration and diffusion of Ca2+.
Lechleiter
J D
JD
Department of Pharmacology, Mayo Foundation, Rochester, Minnesota 55905.
Clapham
D E
DE
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D004058:Diffusion; D019204:GTP-Binding Proteins / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D008845:Microinjections; D008954:Models, Biological; D009865:Oocytes / Q000378:metabolism*; D013696:Temperature; D014982:Xenopus laevis
D016244:Guanosine 5'-O-(3-Thiotriphosphate); D015544:Inositol 1,4,5-Trisphosphate; D019204:GTP-Binding Proteins; D002118:Calcium