Showing papers by "Michael J. Berridge published in 1991"
TL;DR: It is reported here that the InsP3-sensitive store in hepatocytes discharges spontaneously when overloaded with Ca2+.
Abstract: Inositol 1,4,5-trisphosphate (InsP3) functions as a second messenger to mobilize Ca2+ from intracellular reservoirs. The release mechanism displays all-or-none characteristics, that may account for other observations that the InsP3-induced mobilization of Ca2+ is quantal. Quantal release may depend on the sensitivity of the InsP3 receptor being regulated by the Ca2+ concentration in the lumen of the endoplasmic reticulum. We report here that the InsP3-sensitive store in hepatocytes discharges spontaneously when overloaded with Ca2+. The release, which is blocked by heparin, is preceded by an increasing sensitivity of the InsP3 receptor to endogenous InsP3, and is promoted by those sulphydryl reagents (oxidized glutathione and thimerosal) that induce Ca2+ oscillations in intact cells (ref. 8, and T. A. Rooney, D. C. Renard, E. J. Sass and A. P. Thomas, manuscript in preparation). This novel process could have a role in generating both Ca2+ oscillations and Ca2+ waves.
347 citations
TL;DR: A two pool model has been developed to explain how inositol 1,4,5 trisphosphate acts through its specific receptor to create a constant influx of primer calcium made up of calcium released from the Ins(1, 4,5)P3-sensitive pool (ISCS) together with an influx of external calcium.
176 citations
TL;DR: The model based on Ca(2+)-induced Ca2+ release can be extended to incorporate variations in the level of InsP3 as well as desensitization of the InsP 3 receptor; besides accounting for the phenomena described by the minimal model, the extended model might also account for the occurrence of complex Ca2- oscillations.
108 citations
TL;DR: The caffeine- sensitive Ca2+ store in bovine chromaffin cells is largely distinct from the InsP3-sensitive Ca2-sensitive store, and its release mechanism shares characteristics with the ryanodine receptor of muscle cells.
Abstract: We have characterized some properties of the caffeine-sensitive Ca2+ store in bovine chromaffin cells. Addition of 10 mM-caffeine to permeabilized cells that were allowed to sequester Ca2+ in the presence of the precipitating anion pyrophosphate induced a transient rise in free Ca2+ concentration that was blocked by 10 microM-Ruthenium Red. Caffeine was able to release Ca2+ after the InsP3-sensitive Ca2+ pool had been completely emptied, and 10 microM-InsP3 still released Ca2+ in the presence of a high dose (50 mM) of caffeine, indicating that there are selectively sensitive Ca2+ pools in these cells. The progressive hydrolysis of pyrophosphate by a cytosolic pyrophosphatase induced a spontaneous Ca2+ release after a latency. Caffeine prevented this spontaneous Ca2+ release, indicating that the pyrophosphate-sensitive Ca2+ pool was caffeine-sensitive. On varying the free Ca2+ concentration within the caffeine-sensitive pool (by using methylenediphosphonic acid, pyrophosphate or no precipitating anion), we observed that the Ca(2+)-releasing effect of caffeine was dependent on an elevated intraluminal free Ca2+ concentration. In conclusion, the caffeine-sensitive Ca2+ store in bovine chromaffin cells is largely distinct from the InsP3-sensitive Ca2+ store, and its release mechanism shares characteristics with the ryanodine receptor of muscle cells.
73 citations
TL;DR: It can be concluded that this second messenger is not responsible for the inhibitory action of caffeine and the ability of caffeine to abolish oscillations while not affecting the early Ins (1, 4, 5) P3 response is discussed with regard to the two-pool model for generating calcium oscillations.
Abstract: Immature Xenopus oocytes injected with inositol 1,4,5-trisphosphate (Ins(1,4,5) P$\_{3}$) give a complex electrophysiological response comprising an early depolarizing spike followed by a burst of oscillations. These two components have been interpreted on the basis of an interaction between two internal calcium stores: an Ins(1,4,5) P$\_{3}$-sensitive pool responsible for the early spike which then primes an Ins(1,4,5) P$\_{3}$-insensitive pool to begin to oscillate through a process of calcium-induced calcium release (Berridge, M. J., J. Physiol., Lond. 403, 589-599 (1988)). The role of the latter was investigated in Xenopus oocytes by using the drug caffeine which can trigger calcium-induced calcium release in muscle cells. Caffeine had no effect on the early Ins(1,4,5) P$\_{3}$-induced spike but it suppressed the subsequent oscillations. The spontaneous oscillations observed in some oocytes were also abolished by caffeine. Oscillation amplitude and duration was slightly reduced following incubation of oocytes with adenosine or isobutyl-methylxanthine. Because these two agents gave large membrane hyperpolarizations indicative of an increase in cyclic AMP, it can be concluded that this second messenger is not responsible for the inhibitory action of caffeine. The ability of caffeine to abolish oscillations while not affecting the early Ins(1,4,5) P$_{3}$ response is discussed with regard to the two-pool model for generating calcium oscillations.
43 citations
8 citations