CaSiAn: a Calcium Signaling Analyzer tool

Nature reviews. Molecular cell biology, 2000

The universality of calcium as an intracellular messenger depends on its enormous versatility. Cells have a calcium signalling toolkit with many components that can be mixed and matched to create a wide range of spatial and temporal signals. This versatility is exploited to control processes as diverse as fertilization, proliferation, development, learning and memory, contraction and secretion, and must be accomplished within the context of calcium being highly toxic. Exceeding its normal spatial and temporal boundaries can result in cell death through both necrosis and apoptosis.

Current biology, 2002

Recent studies have expanded the number of channel types and messengers that lead to Ca 2+ signals within cells. Furthermore, we are beginning to understand the complex interplay between different sources of Ca 2+ .

Nature, 1998

Ca 2+ signals are a core regulator of plant cell physiology and cellular responses to the environment. The channels, pumps, and carriers that underlie Ca 2+ homeostasis provide the mechanistic basis for generation of Ca 2+ signals by regulating movement of Ca 2+ ions between subcellular compartments and between the cell and its extracellular environment. The information encoded within the Ca 2+ transients is decoded and transmitted by a toolkit of Ca 2+ -binding proteins that regulate transcription via Ca 2+ -responsive promoter elements and that regulate protein phosphorylation. Ca 2+ -signaling networks have architectural structures comparable to scale-free networks and bow tie networks in computing, and these similarities help explain such properties of Ca 2+signaling networks as robustness, evolvability, and the ability to process multiple signals simultaneously. 593 Annu. Rev. Plant Biol. 2010.61:593-620. Downloaded from arjournals.annualreviews.org by University of Delhi on 08/26/10. For personal use only.

Chaos

The universality of Ca 2+ as second messenger in living cells is achieved by a rich spectrum of spatiotemporal cellular concentration dynamics. Ca 2+ release from internal storage compartments plays a key role in shaping cytosolic Ca 2+ signals. Deciphering this signaling mechanism is essential for a deeper understanding of its physiological function and general concepts of cell signaling. Here, we review recent experimental findings demonstrating the stochasticity of Ca 2+ oscillations and its relevance for modeling Ca 2+ dynamics. The stochasticity arises by the hierarchical signal structure that carries molecular fluctuations of single channels onto the level of the cell leading to a stochastic medium as theoretically predicted. The result contradicts the current opinion of Ca 2+ being a cellular oscillator. We demonstrate that cells use array enhanced coherence resonance to form rather regular spiking signals and that the "oscillations" carry information despite the involved stochasticity. The knowledge on the underlying mechanism also allows for determination of intrinsic properties from global observations. In the second part of the paper, we briefly survey different modeling approaches with regard to the experimental results. We focus on the dependence of the standard deviation on the mean period of the oscillations. It shows that limit cycle oscillations cannot describe the experimental data and that generic models have to include the spatial aspects of Ca 2+ signaling.

Proceedings of the National Academy of Sciences, 2011

Metal Ions in Life Sciences, 2012

FEBS Journal, 2009

Calcium ions (Ca 2+) control and influence a diverse array of cellular processes such as muscle contraction, gene expression, energy metabolism, proliferation and cell death. In order to extensively control cellular activity, it is necessary to regulate Ca 2+ signals (changes in Ca 2+ concentration) in 3D space, time and amplitude. Cells normally maintain a low resting 'free' Ca 2+ concentration in the cytosol ([Ca 2+ ] c) of 100 nm. This contrasts with 1 mm in the extracellular fluid of terrestrial animals and 10 mm in seawater. In order to achieve this low resting [Ca 2+ ] c , cells remove Ca 2+ using two energy-dependent mechanisms. First, plasma membrane Ca 2+ ATPases (PMCA) pump Ca 2+ out of the cell against a concentration gradient, consuming ATP in the process. Second, the Na +-Ca 2+ exchanger (NCX) uses the electrochemical Na + gradient; one Ca 2+ being extruded for every three Na + ions entering. In addition, eukaryotic cells can sequester Ca 2+ into intracellular organelles, in particular the endoplasmic reticulum (ER). Organellar Ca 2+ sequestration requires either ATP hydrolysis or a favourable electrochemical gradient. Ca 2+ channels in the plasma membrane or release channels on Ca 2+-containing organelles help deliver Ca 2+ to the required cellular location. This enables the generation of Ca 2+ signals that can be small or large in amplitude, restricted to a small microdomain or global across the cell. Ca 2+ signals can be of variable duration lasting from a few milliseconds to many hours (Fig. 1A). They can either be simple Ca 2+ elevations or

eLS, 2001

The calcium ion (Ca 2+ ) is a versatile intracellular messenger. It provides dynamic regulation of vast array of cellular processes such as gene transcription, differentiation and contraction. Ca 2+ signals range from microsecond, nanoscopic events to intercellular waves lasting for many seconds. This diversity of Ca 2+ signals arises from the wide assortment of Ca 2+ transport and Ca 2+ buffering processes employed by cells. Additional diversity in Ca 2+ signalling stems from the ability of cells to utilise different sources of Ca 2+ . The cytosol is the principal Ca 2+ signalling compartment. When Ca 2+ ions enter the cytosol they interact with numerous Ca 2+ -binding proteins, thereby leading to activation, or inhibition, of cellular processes. Specificity is achieved by regulating the spatial and kinetic properties of Ca 2+ signal. In this way, many concurrent Ca 2+ -sensitive cellular processes can be discretely regulated. A number of pathologies have been related to the breakdown of cellular Ca 2+ homoeostasis or to aberrant Ca 2+ signalling.

Current Biology, 2009