Аннотация
BACKGROUND: Cardiac mechanical and electrical activity are closely
interrelated. While excitation-contraction coupling is rather well
characterized, less is known about cellular mechanisms that promote
mechanically induced changes in cardiac electrical activity--mechano-electric
feedback. OBJECTIVE: To integrate experimental findings on stretch
activation of ion channels and length-dependent changes in intracellular
calcium handling into a mathematical description of cardiac cellular
activity. METHODS: Simulations are based on the cellular OXSOFT HEART
v4.8 models of electrical activity of single cardiac cells of different
populations and species. Sarcolemmal stretch-activated channels,
mechanically induced changes in the affinity of troponin C to calcium,
and length-dependent modulation of calcium handling by the sarcoplasmic
reticulum were introduced into the models and linked to a description
of sarcomere length or isometric tension. RESULTS: Transient or sustained
stretch of cardiomyocytes was simulated during electrical systole
and diastole. The electrophysiological response observed in the model
depended on timing and severity of mechanical stimulation and on
the main subcellular target of the intervention. Responses ranged
from triggering of premature action potentials, over changes in action
potential shape and duration, to length-dependent variations in contractile
behaviour. Modelling findings could be related to experimental observations
and may help to explain some of the contradictory data in the literature.
The model is sufficiently complete to reproduce experimental findings
and to help identify causally linked events.
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