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.

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 [2]

Discovery

Spontaneous Ca2+ sparks were discovered in isolated cardiac muscle cells [3] in 1992 by Peace Cheng and Mark B. Cannell.

Although initially rejected by the journal Nature as artefacts, 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.[4][5] 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

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. 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.
  3. 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.
  4. 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.
  5. 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.

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