Abstract
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.
Highlights
Intrinsic primary afferent neurons (IPANs) in the myenteric plexus comprise an important group of mechanosensory neurons for primary neural control of gastrointestinal motility [1]
Model Estimation on the Morphological Dogiel Type II Neuron. e electrophysiological features of slow after-hyperpolarization (sAHP) and medium after-hyperpolarization (mAHP) neurons with Dogiel type II morphology in the myenteric plexus of pig small intestine were selected for the model optimization (Figures 1(a) and 1(b)). e optimization processes were done by fitting the model to experimentally recorded membrane potential (MP) of the neurons with the injection of rectangular electrical current pulses
Model Estimation of the Neuron During Mechanical Stretch. e MPs from Dogiel type II myenteric neurons of the guinea pig ileum were selected to estimate the model with the mechanosensitive channel current. e MPs were recorded from neurons in a tissue strip under 20% longitudinal stretch and with an injection of 500 ms current pulse
Summary
Intrinsic primary afferent neurons (IPANs) in the myenteric plexus comprise an important group of mechanosensory neurons for primary neural control of gastrointestinal motility [1]. It is a ganglionated network within the myenteric plexus and with projections into the mucosa [2,3,4]. 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. The model successfully predicted the electrophysiological features of the myenteric neurons with and without mechanical stimulation. Conclusions. e model provides a method to predict features and levels of detail of the underlying physiological system in generating myenteric neuron responses. e model could be used as building blocks in future large-scale network simulations of intrinsic primary afferent neurons and their network
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