Ca2+ signalling between single L-type Ca2+ channels and ryanodine receptors in heart cells

Nature. 2001 Mar 29;410(6828):592-6. doi: 10.1038/35069083.


Ca2+-induced Ca2+ release is a general mechanism that most cells use to amplify Ca2+ signals. In heart cells, this mechanism is operated between voltage-gated L-type Ca2+ channels (LCCs) in the plasma membrane and Ca2+ release channels, commonly known as ryanodine receptors, in the sarcoplasmic reticulum. The Ca2+ 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 Ca2+ in the form of Ca2+ sparks. Here we determine the kinetics, fidelity and stoichiometry of coupling between LCCs and ryanodine receptors. We show that the local Ca2+ signal produced by a single opening of an LCC, named a 'Ca2+ sparklet', can trigger about 4-6 ryanodine receptors to generate a Ca2+ 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 Ca2+-signalling mechanisms at the molecular level.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Channels, L-Type / metabolism*
  • Calcium Signaling*
  • In Vitro Techniques
  • Myocardium / cytology
  • Myocardium / metabolism*
  • Patch-Clamp Techniques
  • Rats
  • Ryanodine Receptor Calcium Release Channel / metabolism*
  • Stochastic Processes


  • Calcium Channels, L-Type
  • Ryanodine Receptor Calcium Release Channel
  • Calcium