Mechanisms of Ca$^2+$ release from sarcoplasmic reticulum of
skeletal muscle.
Physiol. Rev., 64 (4):
1240--1320 (October 1984)Abstract
Since the discovery of the ATP-dependent Ca$^2+$ transport by
SR a little over two decades ago, remarkable progress has been made
in understanding the kinetic mechanism of Ca$^2+$ transport and
ATP hydrolysis and the role of phosphorylated enzyme intermediates
in the energetics of active ion transport. Significant information
has accumulated on the structure and composition of the SR membrane,
on the primary amino acid sequence of the Ca$^2+$-pump protein,
and on the adaptive changes in the Ca$^2+$-transport function
during embryonic development and muscle activity. The discovery of
the charge movement as a step in EC coupling and the use of novel
optical probes for analyzing potential and calcium transients in
living muscle changed the enigma of EC coupling into a well-defined
problem that is clearly open to rational solutions. Studies on the
structure, composition, and function of the isolated components of
the T-SR system have just begun. The effectiveness of this approach
will depend on successful maintenance of the functionally intact
structure of the T-SR junction during the disruption of the muscle,
which is required for the isolation of pure membrane elements. Reconstitution
of a functionally competent junctional complex from isolated components
is the ultimate aim of these studies, but the path toward that goal
is so difficult that much of the mechanism of EC coupling may be
solved by electrophysiologists, before reconstitution is achieved.
The avalanche of information on Ca$^2+$ releases induced by various
agents under diverse and sometimes ill-defined conditions led to
formulation of a series of hypothetical mechanisms. Of these, Ca$^2+$-induced
Ca$^2+$ release promises to be an important element of the physiological
Ca$^2+$-release process, but few of the other proposed mechanisms
can be eliminated from consideration at this stage. The impressive
progress of the last few years has left several fundamental problems
largely unsolved. Among these are the physical mode of translocation
of Ca$^2+$ across the membrane and the molecular mechanism of
the coupling of Ca$^2+$ transport to ATP hydrolysis; the regulation
of the concentration of the Ca$^2+$-pump protein and calcium
in the SR of fast and slow skeletal, cardiac, and smooth muscles;
the gating mechanisms that regulate the graded release of calcium
from the SR and the composition and biochemical characterization
of the triad; the role of SR membrane potential in the regulation
of Ca$^2+$ fluxes in vivo; the permeability of SR membranes in
living muscle; the functional significance of protein-protein interactions
in the SR with respect to Ca$^2+$ transport and permeability
control.(ABSTRACT TRUNCATED AT 400 WORDS)
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