%0 Journal Article %1 Wang_2004_3979 %A Wang, Shi Qiang %A Stern, Michael D %A R�os, Eduardo %A Cheng, Heping %D 2004 %J Proc. Natl. Acad. Sci. U. S. A. %K 15004280 Animals, Calcium Calcium, Cardiac, Channel, Confocal, Gov't, Membrane Microscopy, Myocytes, Non-U.S. P.H.S., Patch-Clamp Potentials, Rats, Receptor Release Research Ryanodine Support, Techniques, U.S. %N 11 %P 3979--3984 %R 10.1073/pnas.0306157101 %T The quantal nature of Ca$^2+$ sparks and in situ operation of the ryanodine receptor array in cardiac cells. %U http://dx.doi.org/10.1073/pnas.0306157101 %V 101 %X Intracellular Ca$^2+$ release in many types of cells is mediated by ryanodine receptor Ca$^2+$ release channels (RyRCs) that are assembled into two-dimensional paracrystalline arrays in the endoplasmic/sarcoplasmic reticulum. However, the in situ operating mechanism of the RyRC array is unknown. Here, we found that the elementary Ca$^2+$ release events, Ca$^2+$ sparks from individual RyRC arrays in rat ventricular myocytes, exhibit quantized Ca$^2+$ release flux. Analysis of the quantal property of Ca$^2+$ sparks provided a view of unitary Ca$^2+$ current and gating kinetics of the RyRC in intact cells and revealed that spark activation involves dynamic recruitment of small, variable cohorts of RyRCs. Intriguingly, interplay of RyRCs in multichannel sparks renders an unusual, thermodynamically irreversible mode of channel gating that is unshared by an RyRC acting solo, nor by RyRCs in vitro. Furthermore, an array-based inhibitory feedback, overriding the regenerative Ca$^2+$-induced Ca$^2+$ release of RyRCs, provides a supramolecular mechanism for the microscopic stability of intracellular Ca$^2+$ signaling.

@article{Wang_2004_3979, abstract = {Intracellular {C}a$^{2+}$ release in many types of cells is mediated by ryanodine receptor {C}a$^{2+}$ release channels (Ry{RC}s) that are assembled into two-dimensional paracrystalline arrays in the endoplasmic/sarcoplasmic reticulum. However, the in situ operating mechanism of the Ry{RC} array is unknown. Here, we found that the elementary {C}a$^{2+}$ release events, {C}a$^{2+}$ sparks from individual Ry{RC} arrays in rat ventricular myocytes, exhibit quantized {C}a$^{2+}$ release flux. Analysis of the quantal property of {C}a$^{2+}$ sparks provided a view of unitary {C}a$^{2+}$ current and gating kinetics of the Ry{RC} in intact cells and revealed that spark activation involves dynamic recruitment of small, variable cohorts of Ry{RC}s. Intriguingly, interplay of Ry{RC}s in multichannel sparks renders an unusual, thermodynamically irreversible mode of channel gating that is unshared by an Ry{RC} acting solo, nor by Ry{RC}s in vitro. Furthermore, an array-based inhibitory feedback, overriding the regenerative {C}a$^{2+}$-induced {C}a$^{2+}$ release of Ry{RC}s, provides a supramolecular mechanism for the microscopic stability of intracellular {C}a$^{2+}$ signaling.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Wang, Shi Qiang and Stern, Michael D and R�os, Eduardo and Cheng, Heping}, biburl = {https://www.bibsonomy.org/bibtex/2846d2483dfa0983e9cc3f9cbe93c447d/hake}, description = {The whole bibliography file I use.}, doi = {10.1073/pnas.0306157101}, file = {Wang_2004_3979.pdf:Wang_2004_3979.pdf:PDF}, interhash = {dad20d7891666e954d8ec1724ce1e15a}, intrahash = {846d2483dfa0983e9cc3f9cbe93c447d}, journal = {Proc. Natl. Acad. Sci. U. S. A.}, key = 146, keywords = {15004280 Animals, Calcium Calcium, Cardiac, Channel, Confocal, Gov't, Membrane Microscopy, Myocytes, Non-U.S. P.H.S., Patch-Clamp Potentials, Rats, Receptor Release Research Ryanodine Support, Techniques, U.S.}, month = Mar, number = 11, pages = {3979--3984}, pii = {0306157101}, pmid = {15004280}, timestamp = {2009-06-03T11:21:36.000+0200}, title = {The quantal nature of {C}a$^{2+}$ sparks and in situ operation of the ryanodine receptor array in cardiac cells.}, url = {http://dx.doi.org/10.1073/pnas.0306157101}, volume = 101, year = 2004 }