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Understanding calcium waves and sparks in central neurons.

ABSTRACT: All cells use changes in intracellular calcium concentration ([Ca(2+)](i)) to regulate cell signalling events. In neurons, with their elaborate dendritic and axonal arborizations, there are clear examples of both localized and widespread Ca(2+) signals. [Ca(2+)](i) changes that are generated by Ca(2+) entry through voltage- and ligand-gated channels are the best characterized. In addition, the release of Ca(2+) from intracellular stores can result in increased [Ca(2+)](i); the signals that trigger this release have been less well-studied, in part because they are not usually associated with specific changes in membrane potential. However, recent experiments have revealed dramatic widespread Ca(2+) waves and localized spark-like events, particularly in dendrites. Here we review emerging data on the nature of these signals and their functions.

SUBMITTER: Ross WN

PROVIDER: S-EPMC4501263 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Understanding calcium waves and sparks in central neurons.

Ross William N WN

Nature reviews. Neuroscience 20120208 3

All cells use changes in intracellular calcium concentration ([Ca(2+)](i)) to regulate cell signalling events. In neurons, with their elaborate dendritic and axonal arborizations, there are clear examples of both localized and widespread Ca(2+) signals. [Ca(2+)](i) changes that are generated by Ca(2+) entry through voltage- and ligand-gated channels are the best characterized. In addition, the release of Ca(2+) from intracellular stores can result in increased [Ca(2+)](i); the signals that trigg ...[more]

PMID: 22314443

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Project description:Key pointsIncreasing sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) pump activity enhances sarcoplasmic reticulum calcium (Ca) load, which increases both ryanodine receptor opening and driving force of Ca release flux. Both of these effects promote Ca spark formation and wave propagation. However, increasing SERCA activity also accelerates local cytosolic Ca decay as the wave front travels to the next cluster, which limits wave propagation. As a result, increasing SERCA pump activity has a biphasic effect on the propensity of arrhythmogenic Ca waves, but a monotonic effect to increase Ca spark frequency and amplitude.AbstractWaves of sarcoplasmic reticulum (SR) calcium (Ca) release can cause arrhythmogenic afterdepolarizations in cardiac myocytes. Ca waves propagate when Ca sparks at one Ca release unit (CRU) recruit new Ca sparks in neighbouring CRUs. Under normal conditions, Ca sparks are too small to recruit neighbouring Ca sparks where Ca sensitivity is also low. However, under pathological conditions such as a Ca overload or ryanodine receptor (RyR) sensitization, Ca sparks can be larger and propagate more readily as macro-sparks or full Ca waves. Increasing SERCA pump activity promotes SR Ca load, which promotes RyR opening and increases driving force of the Ca release flux from SR to cytosol, promoting Ca waves. However, high sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) activity can also decrease local cytosolic [Ca] as it approaches the next CRU, thereby reducing wave appearance and propagation. In this study, we use a physiologically detailed model of subcellular Ca cycling and experiments in phospholamban-knockout mice, to show how Ca waves are initiated and propagate and how different conditions contribute to the generation and propagation of Ca waves. We show that reducing diffusive coupling between Ca sparks by increasing SERCA activity prevents Ca waves by reducing [Ca] at the next CRU, as do Ca buffers, low intra-SR Ca diffusion and distance between CRUs. Increasing SR Ca uptake rate has a biphasic effect on Ca wave propagation; initially it enhances Ca spark probability and amplitude and CRU coupling, thereby promoting arrhythmogenic Ca wave propagation, but at higher levels SR Ca uptake can abort those arrhythmogenic Ca waves.

Dataset Information

Understanding calcium waves and sparks in central neurons.

Publications

Understanding calcium waves and sparks in central neurons.

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