A minimal gating model for the cardiac calcium release channel.
Biophys. J., 71 (6):
2996--3012 (December 1996)Abstract
A Markovian model of the cardiac Ca release channel, based on experimental
single-channel gating data, was constructed to understand the transient
nature of Ca release. The rate constants for a minimal gating scheme
with one Ca-free resting state, and with two open and three closed
states with one bound Ca$^2+$, were optimized to simulate the
following experimental findings. In steady state the channel displays
three modes of activity: inactivated 1 mode without openings, low-activity
L mode with single openings, and high-activity H mode with bursts
of openings. At the onset of a Ca$^2+$ step, the channel first
activates in H mode and then slowly relaxes to a mixture of all three
modes, the distribution of which depends on the new Ca$^2+$.
The corresponding ensemble current shows rapid activation, which
is followed by a slow partial inactivation. The transient reactivation
of the channel (increment detection) in response to successive additions
of Ca$^2+$ is then explained by the model as a gradual recruitment
of channels from the extant pool of channels in the resting state.
For channels in a living cell, the model predicts a high level of
peak activation, a high extent of inactivation, and rapid deactivation,
which could underlie the observed characteristics of the elementary
release events (calcium sparks).
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