A detailed, conductance-based computer model of intrinsic sensory neurons of the gastrointestinal tract

Am J Physiol Gastrointest Liver Physiol. 2014 Sep 1;307(5):G517-32. doi: 10.1152/ajpgi.00228.2013. Epub 2014 Jul 10.


Intrinsic sensory neurons (ISNs) of the enteric nervous system respond to stimuli such as muscle tension, muscle length, distortion of the mucosa, and the chemical content in the lumen. ISNs form recurrent networks that probably drive many intestinal motor patterns and reflexes. ISNs express a large number of voltage- and calcium-gated ion channels, some of which are modified by inflammation or repeated physiological stimuli, but how interactions between different ionic currents in ISNs produce both normal and pathological behaviors in the intestine remains unclear. We constructed a model of ISNs including voltage-gated sodium and potassium channels, N-type calcium channels, big conductance calcium-dependent potassium (BK) channels, calcium-dependent nonspecific cation channels (NSCa), intermediate conductance calcium-dependent potassium (IK) channels, hyperpolarization-activated cation (Ih) channels, and internal calcium dynamics. The model was based on data from the literature and our electrophysiological studies. The model reproduced responses to short or long depolarizing current pulses and responses to long hyperpolarizing current pulses. Sensitivity analysis showed that Ih, IK, NSCa, and BK have the largest influence on the number of action potentials observed during prolonged depolarizations. The model also predicts that changes to the voltage of activation for Ih have a large influence on excitability, but changes to the time constant of activation for Ih have a minor effect. Our model identifies how interactions between different iconic currents influence the excitability of ISNs and highlights an important role for Ih in enteric neuroplasticity resulting from disease.

Keywords: computer model; excitability; gastrointestinal tract; intrinsic sensory neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials*
  • Animals
  • Calcium / metabolism
  • Calcium Channels / metabolism
  • Gastrointestinal Tract / innervation*
  • Humans
  • Models, Neurological*
  • Potassium Channels / metabolism
  • Sensory Receptor Cells / metabolism
  • Sensory Receptor Cells / physiology*
  • Voltage-Gated Sodium Channels / metabolism


  • Calcium Channels
  • Potassium Channels
  • Voltage-Gated Sodium Channels
  • Calcium