Simulations of Myenteric Neuron Dynamics in Response to Mechanical Stretch

Background. Intestinal sensitivity to mechanical stimuli has been studied intensively in visceral pain studies. The ability to sense different stimuli in the gut and translate these to physiological outcomes relies on the mechanosensory and transductive capacity of intrinsic intestinal nerves. However, the nature of the mechanosensitive channels and principal mechanical stimulus for mechanosensitive receptors are unknown. To be able to characterize intestinal mechanoelectrical transduction, that is, the molecular basis of mechanosensation, comprehensive mathematical models to predict responses of the sensory neurons to controlled mechanical stimuli are needed. This study aims to develop a biophysically based mathematical model of the myenteric neuron with the parameters constrained by learning from existing experimental data. Findings. The conductance-based single-compartment model was selected. The parameters in the model were optimized by using a combination of hand tuning and automated estimation. Using the optimized parameters, the model successfully predicted the electrophysiological features of the myenteric neurons with and without mechanical stimulation. Conclusions. The model provides a method to predict features and levels of detail of the underlying physiological system in generating myenteric neuron responses. The model could be used as building blocks in future large-scale network simulations of intrinsic primary afferent neurons and their network

Phasic and Tonic Smooth Muscle Function of the Partially Obstructed Guinea Pig Intestine

This study was to generate phasic and tonic stress-strain curves for evaluation of smooth muscle function in the obstructed guinea pig jejunum. Partial and sham obstruction of the jejunum in guinea pigs was created surgically, with guinea pigs not being operated on served as normal controls. The animals survived 2, 4, 7, and 14 days, respectively. The jejunal segment was distended to 10 cm H2O. The pressure and outer diameter changes were recorded. Passive conditions were obtained by using papaverine. Total phasic, tonic, and passive circumferential stress and strain were computed from the diameter and pressure data with reference to the zero-stress-state geometry. The active phasic and tonic stresses were defined as the total phasic and tonic stress minus the passive stress. The thickness of intestinal muscle layers increased in a time-dependent manner after obstruction. The amplitude of passive, total phasic, total tonic, active phasic, and active tonic circumferential stresses increased as function of strain 7 days after obstruction. However, when normalized to muscle layer thickness, the amplitude of active stresses did not differ among the groups. In conclusion, the long-term-obstructed intestine exhibits increased total smooth muscle contraction force. However, the contraction force per smooth muscle unit did not increase