Calcium sparks
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Ca2� sparks, which are small, brief, and highly localized releases of Ca2�, were first observed in cardiac myocytes (27) and then in skeletal muscle fibers (128, 266). They occur spontaneously in frog skeletal muscle fibers in the resting state (128) and at higher frequencies during depolarization (128, 266). The frequency of Ca2� sparks activated by depolarization steeply increases with voltage at �4 mV per e-fold change (128), which is similar to the voltage dependence of the activation of Ca2� release determined in whole fibers (6, 209). Unlike the spark frequency, the spatiotemporal properties of sparks are almost identical at rest and during depolarizations to different potentials (128, 130, 141). The pattern of occurrence of Ca2� sparks after the start of a large depolarization, i.e., the latency histogram of Ca2� sparks, is similar to the pattern of the rate of Ca2� release after depolarization showing Ca inactivation of Ca2� release (129, 130). These results suggest that the Ca2� spark is the basic unit event of physiological Ca2� release. Calcium sparks are calcium release events that occur within muscle cells. They are important in a physiological process called excitation-contraction coupling, which is crucial to muscle function. In essence, electrical stimulation of the outer surface of a muscle cell triggers (via a mechanism dependent on the muscle type) thousands of calcium sparks that spatio-temporally summate to increase intracellular calcium levels.[1] This increase in calcium subsequently activates calcium-sensitive proteins that are responsible for cell-shortening, or contraction.
In muscle, action potentials lead to the opening of intracellular calcium ion channels called ryanodine receptors or RyRs located in the membrane of the sarcoplasmic reticulum (SR). This results in facilitated diffusion of calcium ions from the SR into the sarcoplasm of the muscle cell. The calcium sparks then combine to form a calcium signal. This calcium signal allows the calcium to bind to troponin and initiate contraction.
Though calcium sparks occur as a consequence of muscle electrical excitation, they can also occur spontaneously in a cell at rest. In fact, it was in a resting cardiac muscle cell that calcium sparks that were first discovered.[2] Calcium sparks were discovered in 1992 by Mark B. Cannell and Peace Cheng (a graduate student). This discovery took place in the confocal microscope laboratory set up by Jon W. Lederer, while Mark Cannell was on sabbatical leave from St. George's Hospital Medical School. Although initially rejected by the journal Nature as artefacts, they were quickly recognized as being of fundamental importance to muscle physiology, as both evoked and spontaneous calcium 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 calcium dye used. Calcium “sparks” were termed because of the spontaneous and spatio-temporally localized nature of the calcium release. It may also be notable that these events also led to the sale of a great number of confocal microscopes as only this machine was capable of detecting them at that time.
Because of the importance of calcium sparks in elucidating the gating properties of RyRs in situ, many studies have focussed on improving their detectability in image data. [3][4] It is hoped that by accurately and reliably detecting all calcium spark vents, their true properties can tell us something about the way calcium is released from the SR in the muscle cell.
[edit] See also
[edit] References
- ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1225569.
- ^ Cheng H, Lederer WJ, Cannell MB (October 1993). "Calcium sparks: elementary events underlying excitation-contraction coupling in heart muscle". Science 262 (5134): 740–4. doi:10.1126/science.8235594. PMID 8235594.
- ^ Cheng H, Song LS, Shirokova N, et al. (February 1999). "Amplitude distribution of calcium 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1300067.
- ^ Sebille S, Cantereau A, Vandebrouck C, et al. (January 2005). "Calcium 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.
[edit] External links
Software
- SparkMaster - Automated Calcium Spark Analysis with ImageJ - Free software for calcium spark analysis in confocal linescan images
