The heartbeat is triggered by the release of calcium within cardiac muscle cells. This occurs through specialized channels called Ryanodine Receptors. However, it has remained unclear how these channels collaborate to release calcium. In new work published in Nature Cardiovascular Research, Yufeng Hou and collaborators investigated this critical question. The work was performed within the Louch Group at IEMR, and with collaborators from the University of Bern, Switzerland, and the University of Otago, New Zealand.
For the project, a new mouse was developed which has a special fluorescent label on Ryanodine Receptors. This label allows the positions of the channels to be located with high accuracy in living cells, using advanced (super-resolution) microscopy. Each calcium release event, called a calcium spark, can then be traced to the channels where it originated. Importantly, Hou and colleagues observed that while some calcium sparks are generated by the opening of Ryanodine Receptors within a single cluster, other sparks “travel” between neighbouring clusters of the channels. Further analysis allowed quantification of the number of channels that open during each spark, and it was found that this number varies greatly. Interestingly, during the fight-or-flight response, more channels were observed to open to collaboratively increase calcium release. This work shows that Ryanodine Receptors cooperatively generate calcium sparks, and thus the heartbeat, in a complex and flexible fashion.
Calcium sparks (shown yellow) were linked to the openings of clusters of Ryanodine Receptors (white). The calcium store, called the Sarcoplasmic Reticulum, is shown in red.
Nature Cardiovascular Research