Muscle length-dependent contribution of motoneuron Ca_v1.3 channels to force production in model slow motor unit

Abstract

Persistent inward current (PIC)-generating Ca1.3 channels in spinal motoneuron dendrites are thought to be actively recruited during normal behaviors. However, whether and how the activation of PIC channels influences force output of motor unit remains elusive. Here, building a physiologically realistic model of slow motor unit I demonstrated that force production induced by the PIC activation is much smaller for short than lengthened muscles during the regular firing of the motoneuron that transitions from the quiescent state by either a brief current pulse at the soma or a brief synaptic excitation at the dendrites. By contrast, the PIC-induced force potentiation was maximal for short muscles when the motoneuron switched from a stable low-frequency firing state to a stable high-frequency firing state by the current pulse at the soma. Under the synaptic excitation at the dendrites, however, the force could not be potentiated by the transitioning of the motoneuron from a low- to a high-frequency firing state due to the simultaneous onset of PIC at the dendrites and firing at the soma. The strong dependency of the input-output relationship of the motor unit on the neuromodulation and Ia afferent inputs for the PIC channels was further shown under static variations in muscle length. Taken together, these findings suggest that the PIC activation in the motoneuron dendrites may differentially affect the force production of the motor unit, depending not only on the firing state history of the motoneuron and the variation in muscle length but also on the mode of motor activity. Ca1.3 channels in motoneuron dendrites are actively involved during normal motor activities. To investigate the effects of the activation of motoneuron Ca1.3 channels on force production, a model motor unit was built based on best-available data. The simulation results suggest that force potentiation induced by Ca1.3 channel activation is strongly modulated not only by firing history of the motoneuron but also by length variation of the muscle as well as neuromodulation inputs from the brainstem.

Linking Motoneuron PIC Location to Motor Function in Closed-Loop Motor Unit System Including Afferent Feedback: A Computational Investigation

“…7 and Fig. 8 in (Kim 2017b)). However, the discharge patterns of the motoneuron and the degree of force potentiation (i.e., DFG) considerably differed between two cases.…”

“…Under dendritic excitation condition, the capability of self-sustaining firing (i.e., DCT) and the rate of force development (i.e., 1/DCI) increased with increasing neuromodulatory input from -30 % to 40 % deviation from the default level (see Fig. 8 in (Kim 2017b)) and the neuromodulation effect on the 1/DCI was more obvious for shortened muscles. These results from the previous study were qualitatively similar to those in the present study, in which PIC channels were moved eccentrically away from the soma (i.e., D path of 0 mm to ~1 mm) (compare Fig.…”

“…1). The modeling procedures, model equations and parameter values for the motoneuron and muscle fibers of the motor unit model were fully presented in a previous study (Kim 2017b). In the present study, the efferent and afferent nerves were assumed to perfectly transfer the action potentials from the motoneuron and the muscle spindle and were modeled as a single parameter representing the conduction delay (i.e., 10 ms) over the nerve.…”

“…Functional consequences of neuromodulatory drive versus PIC activation location Recent experimental studies have suggested that the level of neuromodulatory drive from the brain stem may vary depending on the target muscles (Bowker et al 1982;Esposito et al 2014;Powers and Binder 2001) and pathological states (McPherson et al 2018a;McPherson et al 2018b). A recent computational study showed analyzing the open-loop motor unit model how neuromodulatory inputs to motoneurons, including intrinsic inputs from PIC channels at a D path of ~0.6 mm, influence force production by the motor unit during isometric contractions at various muscle lengths (Kim 2017b). Under dendritic excitation condition, the capability of self-sustaining firing (i.e., DCT) and the rate of force development (i.e., 1/DCI) increased with increasing neuromodulatory input from -30 % to 40 % deviation from the default level (see Fig.…”

“…The open-loop motor unit model developed in the previous study was extended for the present study, including the physiological distribution of afferent inputs from the muscle spindle over the motoneuron dendrites. The fundamental limitations of the current modeling approach have been discussed in the previous study (Kim 2017b). For further investigation of the closed-loop motor unit system under physiological intrinsic and extrinsic conditions, the motor unit model presented here should be improved considering the following issues.…”