The local control concept of excitation-contraction coupling in the
heart postulates that the activity of the sarcoplasmic reticulum
ryanodine receptor channels (RyR) is controlled by Ca$^2+$ entry
through adjoining sarcolemmal single dihydropyridine receptor channels
(DHPRs). One unverified premise of this hypothesis is that the RyR
must be fast enough to track the brief (<0.5 ms) Ca$^2+$ elevations
accompanying single DHPR channel openings. To define the kinetic
limits of effective trigger Ca$^2+$ signals, we recorded activity
of single cardiac RyRs in lipid bilayers during rapid and transient
increases in Ca$^2+$ generated by flash photolysis of DM-nitrophen.
Application of such Ca$^2+$ spikes (amplitude approximately 10-30
microM, duration approximately 0.1-0.4 ms) resulted in activation
of the RyRs with a probability that increased steeply (apparent Hill
slope approximately 2.5) with spike amplitude. The time constants
of RyR activation were 0.07-0.27 ms, decreasing with spike amplitude.
To fit the rising portion of the open probability, a single exponential
function had to be raised to a power n approximately 3. We show that
these data could be adequately described with a gating scheme incorporating
four sequential Ca$^2+$-sensitive closed states between the resting
and the first open states. These results provide evidence that brief
Ca$^2+$ triggers are adequate to activate the RyR, and support
the possibility that RyR channels are governed by single DHPR openings.
They also provide evidence for the assumption that RyR activation
requires binding of multiple Ca$^2+$ ions in accordance with
the tetrameric organization of the channel protein.