Abstract
Cardiac excitation-contraction (E-C) coupling describes the process
that links sarcolemmal Ca$^2+$ influx via L-type Ca$^2+$
channels to Ca$^2+$ release from the sarcoplasmic reticulum via
ryanodine receptors (RyRs). This process has proven difficult to
study experimentally, and complete descriptions of how the cell couples
surface membrane and intracellular signal transduction proteins to
achieve both stable and sensitive intracellular calcium release are
still lacking. Mathematical models provide a framework to test our
understanding of how this is achieved. While no single model is yet
capable of describing all features of cardiac E-C coupling, models
of increasing complexity are revealing unexpected subtlety in the
process. In particular, modelling has established a general failure
of 'common-pool' models and has emphasized the requirement for 'local
control' so that microscopic sub-cellular domains can separate local
behaviour from the whole-cell average (common-pool) behaviour. The
micro-architecture of the narrow diadic cleft in which the local
control takes place is a key factor in determining local Ca$^2+$
dynamics. There is still considerable uncertainty about the number
of Ca$^2+$ ions required to open RyRs within the cleft and various
gating models have been proposed, many of which are in reasonable
agreement with available experimental data. However, not all models
exhibit a realistic voltage dependence of E-C coupling gain. Furthermore,
it is unclear which model features are essential to producing reasonable
gain properties. Thus, despite the success of local-control models
in explaining many features of cardiac E-C coupling, more work will
be needed to provide a sound theoretical basis of cardiac E-C coupling.
- 15142741
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- reticulum,
- ryanodine
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