Calcium sparks

Calcium (Ca²⁺) sparks are intracellular Ca²⁺ release events that are important in excitation-contraction coupling. In cardiac muscle cells, a Ca²⁺ spark arises from the activation of a cluster of ryanodine receptors, which causes Ca²⁺ to be released from an intracellular organelle, the sarcoplasmic reticulum. Near synchronous activation of ~ 10⁴ Ca²⁺ sparks produces a cell-wide Ca²⁺ transient that then activates the myofilaments to cause muscle contraction.^[1] Ca²⁺ sparks are important in physiology as they demonstrate how Ca²⁺ can be spatio-temporally compartmentalized to control signalling processes at a sub-cellular level. This is now known as "local control" and is key to the production of graded Ca²⁺ release.^[2]

Activation

During excitation-contraction coupling

The primary mechanism of Ca²⁺ spark activation differs depending on muscle type. For example, in skeletal muscle, ryanodine receptors are physically linked to surface membrane dihydropyridine receptor Ca²⁺ channels so that activation of these channels by membrane depolarization leads to ryanodine receptor activation. By contrast in cardiac muscle, ryanodine receptors are activated by the Ca²⁺ current of activated dihydropyridine receptor Ca²⁺ channels (see Ca²⁺-induced Ca²⁺ release).

Spontaneous release

Ca²⁺ sparks can occur in cells that are not electrically stimulated. The occurrence of 'spontaneous' Ca²⁺ sparks increases with the cell's Ca²⁺ content ^[3]

Discovery

Spontaneous Ca²⁺ sparks were discovered in isolated cardiac muscle cells ^[4] in 1992 by Peace Cheng and Mark B. Cannell in Jon Lederer's laboratory at the University of Maryland in Baltimore, U.S.A.

Although initially rejected by the journal Nature as artifacts, they were quickly recognized as being of fundamental importance to muscle physiology. Indeed, both evoked and spontaneous Ca²⁺ sparks have subsequently been discovered and validated in various tissues, including skeletal and smooth muscles. Their discovery was possible due to the increase in signal contrast provided by the improved axial resolution of the confocal microscope, as well as the fluorescence properties of the fluorescent Ca²⁺ indicator used (fluo-3).

Ca²⁺ “sparks” were so called because of the spontaneous and spatio-temporally localized nature of the Ca²⁺ release and they are the initiation event of excitation-contraction coupling.

Detection and Analysis

Because of the importance of Ca²⁺ sparks in elucidating the gating properties of ryanodine receptors in situ, many studies have focused on improving their detectability in image data.^[5][6] It is hoped that by accurately and reliably detecting all Ca²⁺ spark events, their true properties can tell us something about the way Ca²⁺ is released from the sarcoplasmic reticulum in the muscle cell.

See also

• Confocal microscopy
• Calcium-induced calcium release
• Ryanodine receptor

References

1. Cannell MB, Cheng H, Lederer WJ (November 1994). "Spatial non-uniformities in Ca²⁺_i during excitation-contraction coupling in cardiac myocytes". Biophysical Journal 67 (5): 1942–56. doi:10.1016/S0006-3495(94)80677-0. PMC 1225569. PMID 7858131.
2. Cannell MB, Kong CHT (2012). "Local control in cardiac E–C coupling". Journal of molecular and cellular cardiology 52: 298–303. doi:10.1016/j.yjmcc.2011.04.014.
3. Díaz ME, Trafford AW, O'Neill SC, Eisner DA (May 1997). "Measurement of sarcoplasmic reticulum Ca²⁺ content and sarcolemmal Ca²⁺ fluxes in isolated rat ventricular myocytes during spontaneous Ca²⁺ release". The Journal of Physiology 501 (1): 3–16. doi:10.1111/j.1469-7793.1997.003bo.x.
4. Cheng H, Lederer WJ, Cannell MB (October 1993). "Ca²⁺ sparks: elementary events underlying excitation-contraction coupling in heart muscle". Science 262 (5134): 740–4. doi:10.1126/science.8235594. PMID 8235594.
5. Cheng H, Song LS, Shirokova N; et al. (February 1999). "Amplitude distribution of Ca²⁺ sparks in confocal images: theory and studies with an automatic detection method". Biophysical Journal 76 (2): 606–17. doi:10.1016/S0006-3495(99)77229-2. PMC 1300067. PMID 9929467.
6. Sebille S, Cantereau A, Vandebrouck C; et al. (January 2005). "Ca²⁺ sparks in muscle cells: interactive procedures for automatic detection and measurements on line-scan confocal images series". Computer Methods and Programs in Biomedicine 77 (1): 57–70. doi:10.1016/j.cmpb.2004.06.004. PMID 15639710.

External links

Software

• SparkMaster - Automated Ca²⁺ Spark Analysis with ImageJ - Free software for Ca²⁺ spark analysis in confocal linescan images