Ca$^2+$ signalling between single L-type Ca$^2+$ channels and ryanodine receptors in heart cells.
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Nature 410 (6828): 592--596 (March 2001)

Ca$^2+$-induced Ca$^2+$ release is a general mechanism that most cells use to amplify Ca$^2+$ signals. In heart cells, this mechanism is operated between voltage-gated L-type Ca$^2+$ channels (LCCs) in the plasma membrane and Ca$^2+$ release channels, commonly known as ryanodine receptors, in the sarcoplasmic reticulum. The Ca$^2+$ influx through LCCs traverses a cleft of roughly 12 nm formed by the cell surface and the sarcoplasmic reticulum membrane, and activates adjacent ryanodine receptors to release Ca$^2+$ in the form of Ca$^2+$ sparks. Here we determine the kinetics, fidelity and stoichiometry of coupling between LCCs and ryanodine receptors. We show that the local Ca$^2+$ signal produced by a single opening of an LCC, named a 'Ca$^2+$ sparklet', can trigger about 4-6 ryanodine receptors to generate a Ca$^2+$ spark. The coupling between LCCs and ryanodine receptors is stochastic, as judged by the exponential distribution of the coupling latency. The fraction of sparklets that successfully triggers a spark is less than unity and declines in a use-dependent manner. This optical analysis of single-channel communication affords a powerful means for elucidating Ca$^2+$-signalling mechanisms at the molecular level.
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