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M J Berridge

Publications and source records attributed to M J Berridge.

At least 55 records · Page 3Linked to original sources
PubMed1996

A direct measurement of increased divalent cation influx in fertilised mouse oocytes.

On fertilisation of mouse oocytes, the fusing spermatozoon triggers a series of repetitive calcium (Ca2+) spikes. The Ca2+ spikes seem to be necessary for successful progression through the cell cycle and are regulated in a cell-cycle-dependent manner. The spikes appear to require the linkage of continuous Ca2+ influx to the periodic release of Ca2+ from intracellular stores by a process of Ca(2+)-induced Ca2+ release. The precise role of Ca2+ influx was explored using the manganese (Mn2+)-quench technique to monitor unidirectional cation influx into single mouse oocytes. There was a marked stimulation of cation influx associated closely with the upsweep of the first and subsequent fertilisation Ca2+ spikes. A smaller but significant increase in the rate of cation influx persisted in the interspike period in fertilised oocytes. Spike-associated entry was not as apparent in oocytes stimulated to spike repetitively by thimerosal or acetylcholine application. Instead, there was a continuous increase in cation influx underlying Ca2+ spiking which commenced with the onset of the first spike. Using the specific microsomal inhibitor thapsigargin and the Ca2+ ionophore ionomycin, we found evidence for a capacitative entry mechanism in mouse oocytes. We propose that the persistent influx of Ca2+ observed in response to all stimuli examined is controlled by a capacitative mechanism and sets the frequency of spiking by determining the time taken to refill the internal stores to a point where they are again sensitive enough to initiate the next spike.

Acetylcholine↗
PubMed1995

Putative capacitative calcium entry channels: expression of Drosophila trp and evidence for the existence of vertebrate homologues.

Capacitative calcium entry is a major pathway through which intracellular calcium stores are refilled after stimulation. It has been suggested that the protein encoded by the transient receptor potential (trp) gene expressed in Drosophila photoreceptors may be homologous with capacitative calcium entry channels. Expression of the trp gene product in Xenopus oocytes led to significant increases in calcium entry only when the intracellular calcium stores were depleted. Previous investigations have found trp to be uniquely expressed in Drosophila photoreceptors, but PCR cloning shows that homologous proteins exist in Calliphora, mouse brain and Xenopus oocytes. It is thus possible that capacitative calcium entry in Xenopus oocytes is mediated by a homologue of trp.

Amino Acid Sequence↗
PubMed1995

G-protein regulation of capacitative calcium entry may be mediated by protein kinases A and C in Xenopus oocytes.

Inositol 2,4,5-trisphosphate irreversibly activated capacitative calcium entry in Xenopus oocytes, whereas guanosine thiotriphosphate (GTP[S]) and AIF4- only activated capacitative calcium entry transiently. Both GTP[S] and AIF4- inhibited capacitative calcium entry activated by thapsigargin pretreatment, but guanosine thiodiphosphate (GDP[S]), inositol 2,4,5-trisphosphate and dibutyryl cyclic GMP did not affect capacitative calcium entry. This suggests the involvement of heterotrimeric GTP-binding proteins in the regulation of capacitative calcium entry. Activation of protein kinase C or cyclic-AMP-dependent protein kinase had profound effects on capacitative calcium entry, which were consistent with the hypothesis that the effects of GTP[S] and AIF4- on capacitative calcium entry may be mediated via heterotrimeric GTP-binding protein stimulation of kinases. Further evidence for this hypothesis was derived from the result that the effects of GTP[S] on calcium entry could be inhibited by the application of the protein kinase inhibitor staurosporine.

Adenylyl Cyclases↗
PubMed1995

Calcium signalling and cell proliferation.

The orderly sequence of events that constitutes the cell cycle is carefully regulated. A part of this regulation depends upon the ubiquitous calcium signalling system. Many growth factors utilize the messenger inositol trisphosphate (InsP3) to set up prolonged calcium signals, often organized in an oscillatory pattern. These repetitive calcium spikes require both the entry of external calcium and its release from internal stores. One function of this calcium signal is to activate the immediate early genes responsible for inducing resting cells (G0) to re-enter the cell cycle. It may also promote the initiation of DNA synthesis at the G1/S transition. Finally, calcium contributes to the completion of the cell cycle by stimulating events at mitosis. The role of calcium in cell proliferation is highlighted by the increasing number of anticancer therapies and immunosuppressant drugs directed towards this calcium signalling pathway.

Animals↗
PubMed1994

The regulation of capacitative calcium entry by calcium and protein kinase C in Xenopus oocytes.

Agonists linked to the phosphoinositide signaling pathway evoke capacitative calcium entry in Xenopus oocytes. This entry pathway can also be activated by injection of inositol 2,4,5-trisphosphate, application of thapsigargin, or incubation in calcium-free medium. A variety of protocols revealed highly nonlinear behavior of the calcium entry in thapsigargin-treated oocytes suggestive of positive and negative feedback by calcium at the level of its own entry. These feedback mechanisms may account for the highly damped calcium oscillations we observed in thapsigargin-treated oocytes. Low level activation of protein kinase C potentiated calcium influx in thapsigargin-treated oocytes, apparently by blocking the inactivation of the calcium influx. Higher levels of protein kinase C activity inhibited capacitative calcium entry.

Animals↗
PubMed1994

Overexpression of inositol 1,4,5-trisphosphate 3-kinase in Xenopus oocytes inhibits agonist-evoked capacitative calcium entry.

Ins(1,4,5)P3 3-kinase is a key enzyme in the regulation of Ins(1,4,5)P3. Overexpression of Ins(1,4,5)P3 3-kinase inhibited agonist-evoked and Ins(1,3,4,5)P4-evoked Ca2+ entry in Xenopus oocytes, but did not inhibit Ca2+ entry evoked by thapsigargin or non-metabolizable Ins(1,4,5)P3 analogues. The data suggest that Ins(1,4,5)P3 alone plays the crucial role in the activation of capacitative Ca2+ entry by emptying intracellular stores.

Animals↗
PubMed1994

Smoothly graded Ca2+ release from inositol 1,4,5-trisphosphate-sensitive Ca2+ stores.

Stimulation of cells with Ca(2+)-mobilizing hormones often leads to the generation of temporally and spatially complex changes in the intracellular Ca2+ ion concentration ([Ca2+]i). To understand the mechanisms regulating Ca2+ release from intracellular stores more clearly, we investigated the ability of histamine to release Ca2+ stores under different experimental conditions, using video imaging of single Fura-2-loaded HeLa cells. In Ca(2+)-free medium, stepwise increases in histamine concentration released an increasing proportion of the intracellular Ca2+ pool. This pattern of Ca2+ release is analogous to the "quantal" release of Ca2+ previously observed using permeabilized cells. Quantal Ca2+ release was observed at both 20 and 37 degrees C and was not due to inactivation or desensitization of the Ca2+ release mechanism, since application of histamine in a pulsatile manner, which avoided desensitization of the Ca(2+)-release mechanism, still produced a quantal response. In Ca(2+)-containing medium at both 20 and 37 degrees C, stepwise increases in histamine concentration evoked [Ca2+]i responses where the amplitude was smoothly graded in direct proportion to the histamine concentration. Similar smoothly graded responses were observed from HeLa cells in Ca(2+)-free medium. These data indicate that hormone-evoked Ca2+ release from intracellular stores is limited by the hormone concentration, and that the mechanisms underlying complex [Ca2+]i signals do not lead to an all-or-none release of Ca2+ from the entire intracellular Ca2+ pool. We suggest that the hormone-sensitive intracellular Ca2+ pool is composed of functionally discrete units that are recruited by agonists in a concentration-dependent manner.

Calcium↗
PubMed1994

Relationship between latency and period for 5-hydroxytryptamine-induced membrane responses in the Calliphora salivary gland.

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.

Animals↗
PubMed1994

Quantal Ca2+ mobilization by ryanodine receptors is due to all-or-none release from functionally discrete intracellular stores.

Low caffeine concentrations were unable to completely release the caffeine- and ryanodine-sensitive intracellular Ca2+ pool in intact adrenal chromaffin cells. This 'quantal' Ca2+ release is the same as that previously observed with inositol Ins(1,4,5)P3-induced Ca2+ release. The molecular mechanism underlying quantal Ca2+ release from the ryanodine receptor was investigated using fura-2 imaging of single chromaffin cells. Our data indicate that the intracellular caffeine-sensitive Ca2+ pool is composed of functionally discrete stores, that possess heterogeneous sensitivities to caffeine. These stores are mobilized by caffeine in a concentration-dependent fashion, and, when stimulated, individual stores release their Ca2+ in an 'all-or-none' manner. Such quantal Ca2+ release may be responsible for graded Ca2+ responses in single cells.

Adrenal Medulla↗
PubMed1994

Differences in intracellular calcium signaling after activation of the thrombin receptor by thrombin and agonist peptide in osteoblast-like cells.

Thrombin and the thrombin receptor agonist peptide (TRAP) caused a rise in intracellular calcium concentration ([Ca2+]i) in the human osteoblast-like cell line Saos-2. Striking differences in the [Ca2+]i signals elicited by these agonists were revealed. In cell populations, thrombin induced a transient increase in [Ca2+]i while TRAP caused a biphasic [Ca2+]i response consisting of an initial peak and a sustained plateau phase. In individual cells, thrombin mainly caused a single [Ca2+]i transient while TRAP induced repetitive [Ca2+]i spikes. Neither tyrosine phosphorylation, cAMP-dependent phosphorylation, nor pertussis toxin-sensitive G proteins appeared to be involved in thrombin receptor [Ca2+]i signaling in this cell line. However, the sustained [Ca2+]i response caused by TRAP was converted into a transient, thrombin-like response by pretreatment with serine/threonine phosphatase inhibitors. Pretreatment with the phorbol ester phorbol 12-myristate 13-acetate (PMA) abrogated thrombin receptor [Ca2+]i signaling, and TRAP-induced Ca2+ entry was inhibited by the acute treatment with PMA. In contrast, Ca2+ entry stimulated by thapsigargin was not sensitive to agents affecting serine/threonine phosphorylation. The observation that thrombin and TRAP, despite being agonists for a common receptor, induce dissimilar [Ca2+]i responses indicates that binding of TRAP alone is insufficient to fully regulate the thrombin receptor in Saos-2 cells.

Amino Acid Sequence↗
PubMed1994

The biology and medicine of calcium signalling.

Calcium is a second messenger responsible for regulating a wide range of cellular processes. It is normally presented as brief spikes even in non-excitable cells. The necessity of limiting the period of calcium stimulation to brief bursts may depend upon the fact that prolonged elevation of calcium can be toxic. It can act on endonucleases in the nucleus to trigger programmed cell death. It will be argued that non-lethal effects of elevated calcium can lead to a variety of pathological conditions including hypertension, atherosclerosis, transformation, malignant hyperthermia and possible neural disorders such as spreading depression and manic-depressive illness.

Animals↗
PubMed1994

Spatial and temporal signalling by calcium.

Recent research has shown the importance of the spatial and temporal aspects of calcium signals, which depend upon regenerative properties of the inositol trisphosphate and ryanodine receptors that regulate the release of calcium from internal stores. Initiation sites have been found to spontaneously release calcium, recognized as 'hot spots' or 'sparks', and can trigger a wave that spreads through a process of calcium-induced calcium release.

Animals↗