Elsevier

Cell Calcium

Volume 40, Issues 5–6, November–December 2006, Pages 405-412
Cell Calcium

Calcium microdomains: Organization and function

https://doi.org/10.1016/j.ceca.2006.09.002Get rights and content

Abstract

Microdomains of Ca2+, which are formed at sites where Ca2+ enters the cytoplasm either at the cell surface or at the internal stores, are a key element of Ca2+ signalling. The term microdomain includes the elementary events that are the basic building blocks of Ca2+ signals. As Ca2+ enters the cytoplasm, it produces a local plume of Ca2+ that has been given different names (sparks, puffs, sparklets and syntillas). These elementary events can combine to produce larger microdomains. The significance of these localized domains of Ca2+ is that they can regulate specific cellular processes in different regions of the cell. Such microdomains are particularly evident in neurons where both pre- and postsynaptic events are controlled by highly localized pulses of Ca2+. The ability of single neurons to process enormous amounts of information depends upon such miniaturization of the Ca2+ signalling system. Control of cardiac cell contraction and gene transcription provides another example of how the parallel processing of Ca2+ signalling can occur through microdomains of intracellular Ca2+.

Introduction

The versatility of Ca2+ as an intracellular messenger depends on its spatial and temporal properties. The latter refer to the fact that most Ca2+ signals are delivered as brief transients that often are organized into regular oscillations. Since the frequency of these repetitive transients can be modulated, they encode information to control a large variety of cellular processes. The spatial organization of Ca2+ into distinct microdomains is another way of enhancing the versatility of this signalling system by enabling cells to regulate different processes within localized regions of the cell. In this article, I shall use the general definition of a Ca2+ microdomain as any Ca2+ signalling event that is localized to a specific part of the cell [1]. The many different microdomains that have been described so far are all based on elementary events that can be organized into domains of different sizes. The primary focus will be on the functionality of such domains in regulating specific cellular processes particularly in the case of neurons and cardiac muscle cells.

Section snippets

Elementary events and microdomains

Elementary events are produced by the opening of a single or a small group of Ca2+ channels located in either the plasma membrane or in the endoplasmic/sarcoplasmic reticulum (ER/SR). The Ca2+ that flows into the cytoplasm forms a localized plume of Ca2+ that has been visualized in a number of different cells [1], [2], [3]. These elementary events have been given different names depending on the channels responsible for their formation (Fig. 1).

Ca2+ microdomains and neural function

The functional significance of Ca2+ microdomains is particularly well illustrated in neurons where a number of different cellular processes are regulated by highly localized pulses of Ca2+ (Fig. 2). In the case of neurons that have spiny dendrites, such as hippocampal and Purkinje neurons, Ca2+ signals are confined to the spines and this contributes to the processes of input-specific signalling. Aspiny dendrites of neocortical fast spiking interneurons that lack spines also have localized

Ca2+ microdomains and cardiac function

Microdomains of Ca2+ play a major role in regulating the contraction of cardiac cells. The way in which Ca2+ signalling is organized is very different in ventricular and atrial cells (Fig. 3). In both cases, microdomains of Ca2+ are used to create the global signal that drives contraction, but the mode of recruitment is different. In the case of atrial cells, Ca2+ sparks are generated at the junctional zones where the junctional sarcoplasmic reticulum (jSR) lies close to the sarcolemma. This

Cardiac hypertrophy and heart disease

A number of signalling pathways have been implicated in the activation of cardiac hypertrophy. One of the characteristics of this hypertrophy is that it proceeds through a process of de-differentiation in that hypertrophic stimuli activate a programme of foetal cardiac gene transcription. Many of the extrinsic factors that drive this hypertrophic response (e.g. mechanical load, loss of myocytes and endocrine factors such as endothelin) seem to act through the Ca2+ signalling system, which

Conclusion

The versatility of Ca2+ signalling is greatly enhanced through the operation of microdomains. These microdomains can vary in size. They include the elementary events that form during the opening of channels in the plasma membrane or internal stores. If such channels are concentrated in a particular region of the cell, these elementary events can sum to generate larger microdomains as might occur for nuclear Ca2+ signals in cardiac cells. The functional significance of microdomains is

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