A mathematical model for β1-adrenergic regulation of the mouse ventricular myocyte contraction.

A mathematical model for β1-adrenergic regulation of the mouse ventricular myocyte contraction. Am J Physiol Heart Circ Physiol. 2019 Dec 13;: Authors: Mullins PD, Bondarenko VE Abstract The β1-adrenergic regulation of cardiac myocyte contraction plays an important role in regulating heart function. Activation of this system leads to an increased heart rate and stronger myocyte contraction. However, chronic stimulation of the β1-adrenergic signaling system can lead to cardiac hypertrophy and heart failure. To understand the mechanisms of action of β1-adrenoceptors, a mathematical model of cardiac myocyte contraction which includes the β1-adrenergic system was developed and studied. The model was able to simulate major experimental protocols for measurements of steady-state force-calcium relationships, cross-bridge release rate (krel) and force development rate (kdf), force-velocity relationship, and force redevelopment rate (ktr). It also reproduced quite well frequency and isoproterenol dependencies for [Ca2+]i transients, total contraction force, and sarcomere shortening. The mathematical model suggested the mechanisms of increased contraction force and myocyte shortening upon stimulation of β1-adrenergic receptors is due to phosphorylation of troponin I and myosin-binding protein C and increased [Ca2+]i transient resulting from activation of the β1-adrenergic signaling system. The model was used to simulate work-loop contra...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research