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M J Berridge

Publications and source records attributed to M J Berridge.

At least 181 records · Page 10Linked to original sources
PubMedDate not supplied

Cytoplasmic calcium oscillations: a two pool model.

Cytosolic calcium oscillations induced by a wide range of agonists, particularly those which stimulate phosphoinositide metabolism, are the result of a periodic release of stored calcium. The formation of inositol 1,4,5 trisphosphate (Ins(1,4,5)P3) seems to play an important role because it can initiate this periodic behaviour when injected or perfused into a variety of cells. A two pool model has been developed to explain how Ins(1,4, 5)P3 sets up these calcium oscillations. It is proposed that Ins(1,4,5)P3 acts through its specific receptor to create a constant influx of primer calcium (Ca2+p) made up of calcium released from the Ins(1,4,5)P3-sensitive pool (ISCS) together with an influx of external calcium. This Ca2+p fails to significantly elevate cytosolic calcium because it is rapidly sequestered by the Ins(1,4,5)P3-insensitive (IICS) stores of calcium distributed throughout the cytosol. Once the latter have filled, they are triggered to release their stored calcium through a process of calcium-induced calcium release to give a typical calcium spike (Ca2+s). In many cells, each Ca2+s begins at a discrete initiation site from which it then spreads through the cell as a wave. The two pool model can account for such waves if it is assumed that calcium released from one IICS diffused across to excite its neighbours thereby setting up a self-propagating wave based on calcium-induced calcium release.

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PubMedDate not supplied

Signal-induced Ca2+ oscillations: properties of a model based on Ca(2+)-induced Ca2+ release.

We consider a simple, minimal model for signal-induced Ca2+ oscillations based on Ca(2+)-induced Ca2+ release. The model takes into account the existence of two pools of intracellular Ca2+, namely, one sensitive to inositol 1,4,5 trisphosphate (InsP3) whose synthesis is elicited by the stimulus, and one insensitive to InsP3. The discharge of the latter pool into the cytosol is activated by cytosolic Ca2+. Oscillations in cytosolic Ca2+ arise in this model either spontaneously or in an appropriate range of external stimulation; these oscillations do not require the concomitant, periodic variation of InsP3. The following properties of the model are reviewed and compared with experimental observations: (a) Control of the frequency of Ca2+ oscillations by the external stimulus or extracellular Ca2+; (b) correlation of latency with period of Ca2+ oscillations obtained at different levels of stimulation; (c) effect of a transient increase in InsP3; (d) phase shift and transient suppression of Ca2+ oscillations by Ca2+ pulses, and (e) propagation of Ca2+ waves. It is shown that on all these counts the model provides a simple, unified explanation for a number of experimental observations in a variety of cell types. 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 InsP3 receptor; besides accounting for the phenomena described by the minimal model, the extended model might also account for the occurrence of complex Ca2+ oscillations.

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PubMedDate not supplied

Functional InsP3 receptors that may modulate excitation-contraction coupling in the heart.

The roles of the Ca2+-mobilising messenger inositol 1,4,5-trisphosphate (InsP3) in heart are unclear, although many hormones activate InsP3 production in cardiomyocytes and some of their inotropic, chronotropic and arrhythmogenic effects may be due to Ca2+ release mediated by InsP3 receptors (InsP3Rs) [1-3]. In the present study, we examined the expression and subcellular localisation of InsP3R isoforms, and investigated their potential role in modulating excitation-contraction coupling (EC coupling). Western, PCR and InsP3-binding analysis indicated that both atrial and ventricular myocytes expressed mainly type II InsP3Rs, with approximately sixfold higher levels of InsP3Rs in atrial cells. Co-immunostaining of atrial myocytes with antibodies against type II ryanodine receptors (RyRs) and type II InsP3Rs revealed that the latter were arranged in the subsarcolemmal space where they largely co-localised with the junctional RyRs. Stimulation of quiescent or electrically paced atrial myocytes with a membrane-permeant InsP3 ester, which enters cells and directly activates InsP3Rs, caused the appearance of spontaneous Ca2+-release events. In addition, in paced cells, the InsP3 ester evoked an increase in the amplitudes of action potential-evoked Ca2+ transients. These data indicate that atrial cardiomyocytes express functional InsP3Rs, and that these channels could modulate EC coupling.

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