Intrafusal cross-bridge dynamics shape history-dependent muscle spindle responses to stretch. 2024

Surabhi N Simha, and Lena H Ting
Wallace H. Coulter Department of Biomedical Engineering, Emory University and The Georgia Institute of Technology, Atlanta, Georgia, USA.

Computational models can be critical to linking complex properties of muscle spindle organs to the sensory information that they encode during behaviours such as postural sway and locomotion where few muscle spindle recordings exist. Here, we augment a biophysical muscle spindle model to predict the muscle spindle sensory signal. Muscle spindles comprise several intrafusal muscle fibres with varied myosin expression and are innervated by sensory neurons that fire during muscle stretch. We demonstrate how cross-bridge dynamics from thick and thin filament interactions affect the sensory receptor potential at the spike initiating region. Equivalent to the Ia afferent's instantaneous firing rate, the receptor potential is modelled as a linear sum of the force and rate change of force (yank) of a dynamic bag1 fibre and the force of a static bag2/chain fibre. We show the importance of inter-filament interactions in (i) generating large changes in force at stretch onset that drive initial bursts and (ii) faster recovery of bag fibre force and receptor potential following a shortening. We show how myosin attachment and detachment rates qualitatively alter the receptor potential. Finally, we show the effect of faster recovery of receptor potential on cyclic stretch-shorten cycles. Specifically, the model predicts history-dependence in muscle spindle receptor potentials as a function of inter-stretch interval (ISI), pre-stretch amplitude and the amplitude of sinusoidal stretches. This model provides a computational platform for predicting muscle spindle response in behaviourally relevant stretches and can link myosin expression seen in healthy and diseased intrafusal muscle fibres to muscle spindle function.

UI MeSH Term Description Entries
D009218 Myosins A diverse superfamily of proteins that function as translocating proteins. They share the common characteristics of being able to bind ACTINS and hydrolyze MgATP. Myosins generally consist of heavy chains which are involved in locomotion, and light chains which are involved in regulation. Within the structure of myosin heavy chain are three domains: the head, the neck and the tail. The head region of the heavy chain contains the actin binding domain and MgATPase domain which provides energy for locomotion. The neck region is involved in binding the light-chains. The tail region provides the anchoring point that maintains the position of the heavy chain. The superfamily of myosins is organized into structural classes based upon the type and arrangement of the subunits they contain. Myosin ATPase,ATPase, Actin-Activated,ATPase, Actomyosin,ATPase, Myosin,Actin-Activated ATPase,Actomyosin ATPase,Actomyosin Adenosinetriphosphatase,Adenosine Triphosphatase, Myosin,Adenosinetriphosphatase, Actomyosin,Adenosinetriphosphatase, Myosin,Myosin,Myosin Adenosinetriphosphatase,ATPase, Actin Activated,Actin Activated ATPase,Myosin Adenosine Triphosphatase
D009470 Muscle Spindles Skeletal muscle structures that function as the MECHANORECEPTORS responsible for the stretch or myotactic reflex (REFLEX, STRETCH). They are composed of a bundle of encapsulated SKELETAL MUSCLE FIBERS, i.e., the intrafusal fibers (nuclear bag 1 fibers, nuclear bag 2 fibers, and nuclear chain fibers) innervated by SENSORY NEURONS. Muscle Stretch Receptors,Neuromuscular Spindles,Receptors, Stretch, Muscle,Stretch Receptors, Muscle,Muscle Spindle,Muscle Stretch Receptor,Neuromuscular Spindle,Receptor, Muscle Stretch,Receptors, Muscle Stretch,Spindle, Muscle,Spindle, Neuromuscular,Spindles, Muscle,Spindles, Neuromuscular,Stretch Receptor, Muscle
D011984 Sensory Receptor Cells Specialized afferent neurons capable of transducing sensory stimuli into NERVE IMPULSES to be transmitted to the CENTRAL NERVOUS SYSTEM. Sometimes sensory receptors for external stimuli are called exteroceptors; for internal stimuli are called interoceptors and proprioceptors. Nerve Endings, Sensory,Neurons, Sensory,Neuroreceptors,Receptors, Neural,Neural Receptors,Receptors, Sensory,Sensory Neurons,Sensory Receptors,Nerve Ending, Sensory,Neural Receptor,Neuron, Sensory,Neuroreceptor,Receptor Cell, Sensory,Receptor Cells, Sensory,Receptor, Neural,Receptor, Sensory,Sensory Nerve Ending,Sensory Nerve Endings,Sensory Neuron,Sensory Receptor,Sensory Receptor Cell
D012518 Sarcomeres The repeating contractile units of the MYOFIBRIL, delimited by Z bands along its length. Sarcomere
D018485 Muscle Fibers, Skeletal Large, multinucleate single cells, either cylindrical or prismatic in shape, that form the basic unit of SKELETAL MUSCLE. They consist of MYOFIBRILS enclosed within and attached to the SARCOLEMMA. They are derived from the fusion of skeletal myoblasts (MYOBLASTS, SKELETAL) into a syncytium, followed by differentiation. Myocytes, Skeletal,Myotubes,Skeletal Myocytes,Skeletal Muscle Fibers,Fiber, Skeletal Muscle,Fibers, Skeletal Muscle,Muscle Fiber, Skeletal,Myocyte, Skeletal,Myotube,Skeletal Muscle Fiber,Skeletal Myocyte

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